9-(2-methylphenyl)-3,4,5,6,9,10-hexahydroxanthene-1,8(2H,7H)-dione

Article abstract of DOI:10.1023/A:1009583417391

Several 9-(2-R phenyl)xanthenediones have been synthesized and the x-ray diffraction structure for the 2-methylphenyl derivative (4b) has been determined. This compound crystallizes in the monoclinic system, space group P2₁/n, with a = 11.729 (

Full text of DOI:10.1023/A:1009583417391

Journal of Chemical Crystallography, Vol. 29, No. 7, 1999
9
1
-(2-Methylphenyl)-3,4,5,6,9,10-hexahydroxanthene-
,8(2H,7H)-dione
(
1)
(1)
(1)
Marco Brito-Arias, Manuel Tapia-Albarr a´ n, Itzia Padilla-Mart ı´ nez, Francisco
(3)
(
1)
(2)
(3)
Mart ı´ nez-Mart ı´ nez, Georgina Espinosa, Elies Molins, * and Enrique Espinosa
Received August 6, 1998
Several 9-(2-R phenyl)xanthenediones have been synthesized and the x-ray diffraction struc-
ture for the 2-methylphenyl derivative (4b) has been determined. This compound crystallizes
in the monoclinic system, space group P2
1
/n, with a ϭ 11.729 (3), b ϭ 9.674 (3), c ϭ 14.628
˚
(4) A, and ͱ ϭ 106.30Њ. It presents a partially hydrogenated xanthene system in distorted boat
conformation for the heterocyclic central ring, and an almost ideal envelope conformation for
the outer rings. The aromatic substituent at the ninth position is at 84Њ in angle with the
xanthene system.
KEY WORDS: X-ray diffraction; xanthenedione; heterocyclic fused rings.
Experimental section
Our general approach uses 1,3-cyclohexanedi-
one (1) and ortho substituted benzaldehydes (2a–d)
as starting materials, which were condensed with
KOH in EtOHUH O media to generate intermedi-
2
ate (3), which is further reacted with sodium methox-
ide solution at room temperature to afford (4). This
reaction can also be carried out straightforwardly by
reacting (1) and (2) with sodium methoxide solution
1
to directly produce (4) in 60% yield. The H NMR
spectroscopy displays similar signal pattern in
agreement with the X-ray structure obtained. Thus,
for (4b) (CDCl ): ͳ 2.0 (4H, t), 2.3 (4H, m), 2.7 (4H,
3
t), 2.9 (3H, s), 5.0 (1H, s), 7.0–7.6 (4H, m). It is
noteworthy to mention that the dimeric intermediate
(
3), which we have been able to isolate, is a key
intermediate for the preparation of the heterocyclic
(
1)
Unidad Profesional Interdisciplinaria de Biotecnolog ı´ a-IPN, Av.
Acueducto s/n Col. Barrio la Laguna Ticom a´ n CP 07340, M e´ xico
DF, M e´ xico.
Instituto de Qu ´ı mica-UNAM, Circuito Exterior Ciudad Uni-
versitaria Coyoac a´ n 04510 M e´ xico DF, M e´ xico.
Institut de Ci e` ncia de Materials de Barcelona (CSIC), Campus
de la UAB, 08193 Bellaterra, Spain.
(
2)
3)
(
Scheme. Reagents and conditions: (i) KOH/EtOH-H
2h; (ii) MeONa/MeOH, RT, 3h; (iii) NaN -HC1/THF, RT, 3h;
(iv) Fe-AcOH/CH Cl , RT, 3h.
2
O, reflux,
3
*
To whom correspondence should be addressed.
2
2
759
1074-1542/99/0700-0759$16.00/0  1999 Plenum Publishing Corporation

760
Brito-Arias et al.
4
Table 1. Crystal Data and Structure Refinement
Table 2. Fractional Atomic Coordinates (ϫ10 ) and Equivalent
˚
3
Isotropic Displacement Coefficients (A ϫ 10 ) for the Title
Empirical formula
CCDC deposit no.
Formula weight
Temperature (K)
Crystal system
C
20
H
20
O
3
Compound
CCDC-1003/5630
308.4
298 (2)
Monoclinic
1
P2 /n
a
x
y
z
U(eq)
C(1)
O(1)
C(2)
C(3)
C(4)
C(4A)
C(4B)
C(5)
C(6)
C(7)
C(8)
6460(2)
6817(2)
6506(3)
5658(3)
5743(2)
5728(2)
5590(2)
5421(3)
5200(3)
6124(3)
6248(2)
6658(2)
5894(2)
5934(2)
6005(2)
5395(2)
4836(2)
4915(2)
3860(3)
2772(2)
2691(2)
3723(2)
6083(3)
Ϫ610(3)
572(2)
4525(2)
4614(1)
5383(2)
5183(2)
4333(2)
3516(1)
1879(1)
1063(2)
133(2)
51(1)
77(1)
71(1)
74(1)
52(1)
41(1)
42(1)
58(1)
65(1)
57(1)
43(1)
60(1)
38(1)
36(1)
39(1)
49(1)
35(1)
42(1)
53(1)
58(1)
56(1)
43(1)
63(1)
Space group
Unit cell dimensions
Ϫ1514(3)
Ϫ2697(3)
Ϫ3521(3)
Ϫ2584(2)
Ϫ2641(2)
Ϫ3620(3)
Ϫ2813(3)
Ϫ1699(3)
Ϫ757(2)
Ϫ397(2)
Ϫ1314(2)
Ϫ363(2)
Ϫ1244(2)
Ϫ3282(2)
Ϫ579(2)
2025(2)
˚
a ϭ 11.729 (3) A Ͱ ϭ 90.0Њ
˚
b ϭ 9.674 (3) A ͱ ϭ 106.30 (2)Њ
˚
c ϭ 14.628 (4) A Ͳ ϭ 90.0Њ
Volume
˚
3
V ϭ 1593.1 (8) A
4
1.286 mg/m
0.085 mm
Siemens P4/PC; ␪/2␪
MoKͰ (graphite monochrom.)/ O(8)
Z
3
Density (calc.)
Ϫ1
Absorption coefficient
Diffractometer/scan
Radiation/wavelength
214(2)
1059(2)
1088(1)
1880(1)
2706(1)
3577(1)
2663(1)
2445(1)
2415(1)
2119(2)
1862(2)
1902(2)
2188(2)
2673(2)
˚
␭
ϭ 0.71073 A
C(8A)
C(9)
F(000)
Crystal size (mm)
656
0.78 ϫ 0.66 ϫ 0.56
2.0 to 27.5Њ
C(9A)
O(10)
C(1Ј)
C(2Ј)
C(3Ј)
C(4Ј)
C(5Ј)
C(6Ј)
C(7Ј)
␪
range for data collec-
tion
Index ranges
0 Յ h Յ 15; 0 Յ k Յ 12;
Ϫ19 Յ l Յ 18
3842
3666 (Rint ϭ 0.0277)/2430
([I Ͼ 2␴(I)])
Semi-empirical
2783(3)
2157(3)
737(3)
Ϫ42(2)
Reflections collected
Independent/observed
refls.
Absorption correction
Max. and min. trans-
mission
Refinement method
Computing
Data/parameters
2774(3)
0.9538 and 0.9364
a
U(eq) is defined as one third of the trace of the orthogonalized
Full matrix least-squares on F2
SHELXTL PLUS (PC version)
3666/209
ij
U tensor.
2
Goodness-of-fit on F
1.034
Final R indices
R1 ϭ 0.0588, wR2 ϭ 0.1673
Results and discussion
[I Ͼ 2␴(I)]
R indices (all data)
Extinction coefficient
Largest diff. peak and hole
R1 ϭ 0.0877, wR2 ϭ 0.1926
We previously reported the synthesis and X-ray
0.006(3)
1
2
structure of acridindione (5) and acridone (6) deriv-
atives, which have been indicated as potential acetil-
cholinesterease inhibitors in the treatment of Alzhei-
˚
Ϫ3
0.78 and Ϫ0.30 eA
3
4
mer and Malaria disease. In continuation of our
studies oriented in preparing heterocyclic three-ring
dione systems, herein we describe the synthesis of
series of 9-(2-R phenyl)xanthenediones (4a–d) and
the tridimensional analysis for the 2-methylphenyl
derivative (4b) referred to above.
Fractional atomic coordinates for non-hydrogen
atoms of the title compound are given in Table 2.
Bond lengths and angles are given in Table 3. The
molecular structure (Fig. 1) can be described as a
xanthenedione group bonded to a methylphenyl sub-
stituent. The xanthene system is roughly planar
(mean planes define angles of 8.0, 10.2, and 8.0Њ be-
tween the central and the outer rings, and between
the outer rings, respectively). The aromatic substitu-
ent is almost perpendicular to the xanthenedione
group, as indicated by the angle between their mean
three ring systems (4), (5), and (6) that we have re-
ported so far. Therefore, depending on the system
requested (either the xanthendione (4), the acridindi-
one (5), or the acridone (6) derivatives), the interme-
diate (3) must be treated with sodium methoxide
solution, with amines or sodium azide, and with iron
in acid, respectively.
The structure of the title compound was solved
by direct methods. Refinement was based on full-
matrix least-squares methods, with anisotropic dis-
placement parameters for all non-H atoms and a
global fixed isotropic displacement parameter for H
atoms. H atoms were included at calculated positions,
using a riding model. Table 1 shows crystal data and
the structure refinement parameters corresponding
to the x-ray diffraction analysis.

9-(2-R phenyl)xanthene-1,8(2H,7H)-dione
761
˚
Table 3. Bond Lengths (A) and Angles (Њ)
C(1)UO(1)
C(1)UC(9A)
C(1)UC(2)
C(2)UC(3)
C(3)UC(4)
C(4)UC(4A)
C(4A)UC(9A)
C(4A)UO(10)
C(4B)UC(8A)
C(4B)UO(10)
C(4B)UC(5)
C(5)UC(6)
1.212(3)
1.472(3)
1.518(3)
1.491(5)
1.505(4)
1.495(3)
1.334(3)
1.375(3)
1.333(3)
1.379(3)
1.492(3)
1.526(4)
1.509(4)
1.510(3)
1.211(3)
1.478(3)
1.508(3)
1.516(3)
1.536(3)
1.388(3)
1.403(3)
1.398(3)
1.502(3)
1.366(4)
1.379(4)
1.387(3)
C(9A)UC(4A)UO(10)
122.7(2)
126.0(2)
111.3(2)
122.6(2)
126.0(2)
111.4(2)
109.9(2)
110.9(2)
113.4(2)
120.4(2)
122.1(2)
117.4(2)
119.1(2)
122.5(2)
118.4(2)
108.2(2)
109.1(2)
112.7(2)
119.0(2)
122.3(2)
118.6(2)
117.6(2)
119.2(2)
118.0(2)
122.7(2)
118.2(2)
119.4(2)
122.5(2)
122.0(2)
120.0(2)
119.3(2)
121.4(2)
C(9A)UC(4A)UC(4)
O(10)UC(4A)UC(4)
C(8A)UC(4B)UO(10)
C(8A)UC(4B)UC(5)
O(10)UC(4B)UC(5)
C(4B)UC(5)UC(6)
C(7)UC(6)UC(5)
C(6)UC(7)UC(8)
O(8)UC(8)UC(8A)
O(8)UC(8)UC(7)
C(8A)UC(8)UC(7)
C(4B)UC(8A)UC(8)
C(4B)UC(8A)UC(9)
C(8)UC(8A)UC(9)
C(8A)UC(9)UC(9A)
C(8A)UC(9)UC(1Ј)
C(9A)UC(9)UC(1Ј)
C(4A)UC(9A)UC(1)
C(4A)UC(9A)UC(9)
C(1)UC(9A)UC(9)
C(4A)UO(10)UC(4B)
C(6Ј)UC(1Ј)UC(2Ј)
C(6Ј)UC(1Ј)UC(9)
C(2Ј)UC(1Ј)UC(9)
C(3Ј)UC(2Ј)UC(1Ј)
C(3Ј)UC(2Ј)UC(7Ј)
C(1Ј)UC(2Ј)UC(7Ј)
C(4Ј)UC(3Ј)UC(2Ј)
C(3Ј)UC(4Ј)UC(5Ј)
C(4Ј)UC(5Ј)UC(6Ј)
C(5Ј)UC(6Ј)UC(1Ј)
C(6)UC(7)
C(7)UC(8)
C(8)UO(8)
C(8)UC(8A)
C(8A)UC(9)
C(9)UC(9A)
C(9)UC(1Ј)
C(1Ј)UC(6Ј)
C(1Ј)UC(2Ј)
C(2Ј)UC(3Ј)
C(2Ј)UC(7Ј)
C(3Ј)UC(4Ј)
C(4Ј)UC(5Ј)
C(5Ј)UC(6Ј)
O(1)UC(1)UC(9A)
O(1)UC(1)UC(2)
C(9A)UC(1)UC(2)
C(3)UC(2)UC(1)
C(2)UC(3)UC(4)
C(4A)UC(4)UC(3)
121.1(2)
121.6(2)
117.3(2)
114.4(2)
111.9(2)
110.5(2)
planes (84Њ) and is shown in the unit cell view (Fig.
). The mean Csp2UCsp2 bond length within the planar
2
˚
phenyl ring of the substituent is 1.39 (1) A.
The molecules are held together by weak
CUHиииO and CUHиииȏ-ring interactions (the
shortest hydrogen bond has d(CиииO) ϭ 3.350(4) A
and d(HиииO) ϭ 2.59 A), which contribute to the
5
˚
˚
stabilization of the molecular and crystal structure.
The shortest contacts are given in Table 4.
1
By comparing the acridindione derivative re-
cently reported with the present xanthenedione com-
pound, we observe a high homology in terms of con-
formation. The outer rings of both the acridine
moiety and the xanthene group have an almost ideal
6
envelope conformation (with puckering parameters :
˚
Q ϭ 0.462 and 0.435 A, ␪ ϭ 123.5 and 121.5Њ, ␸ ϭ
˚
3
00.6 and 298.8Њ, and Q ϭ 0.472 and 0.471 A, ␪ ϭ
120.0 and 119.8Њ, and ␸ ϭ 302.8 and 302.3Њ, for the
acridindione and xanthenedione derivatives, respec-
tively). Also, in both cases, the heterocyclic central
ring presents a distorted boat conformation (Q ϭ
Fig. 1.

762
Brito-Arias et al.
Fig. 2.
˚
a
Table 4. Shortest Intermolecular Contacts (in A and Њ)
DUHиииA
DUH
HиииA
DиииA
DUHиииA
C(6)UH(6A)иииO(8) #1
0.96
2.59
3.350(4)
136
DUHиииCg (Ring)
C(2)UH(2A)иииCg(A.S.) #2
C(7)UH(7A)иииCg(A.S.) #1
HиииCg
2.97
2.75
H-Perp
2.91
2.74
Ͳ
11.2
4.8
DиииCg
3.720
3.506
DUHиииCg
136
136
a
Cg(A.S.) is the center of gravity of the aromatic substituent ring, H-Perp. is the distance from the hydrogen to the ring and Ͳ is the
angle between the H иии Cg direction and the normal to the ring. Symmetry transformations used to generate equivalent atoms are: #1:
1
Ϫ x, Ϫy, Ϫz; #2: 1 Ϫ x, Ϫy, 1 Ϫ z.

9-(2-R phenyl)xanthene-1,8(2H,7H)-dione
763
˚
0
.094 and 0.213 A, ␪ ϭ 103.8 and 101.0Њ, and ␸ ϭ 352.4
References
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derivatives, respectively).
1
2
3
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Acknowledgments
4
.
We are grateful to Dr. Francisco Delgado
ENCB-IPN for NMR determination, to CONACYT
for financial support, and grant (1574P-9507) to M. T.
3
429.
5
.
Desiraju, G.R. Acc. Chem. Res. 1991, 24, 290.
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