11-Butyl-3-meth­oxy-11H-benzo[a]carbazole

Yavuz Ergün; Cevher Gündoğdu; Barış Tercan; Emel Ermiş; Tuncer Hökelek

doi:10.1107/S1600536810021963

. 2010 Jun 16;66(Pt 7):o1634–o1635. doi: 10.1107/S1600536810021963

11-Butyl-3-methoxy-11H-benzo[a]carbazole

Yavuz Ergün ^a, Cevher Gündoğdu ^a, Barış Tercan ^b, Emel Ermiş ^c, Tuncer Hökelek ^d,^*

PMCID: PMC3007054 PMID: 21587864

Abstract

The title compound, C₂₁H₂₁NO, consists of a carbazole skeleton with a methoxybenzene ring fused to the carbazole, and a butyl group attached to the carbazole N atom. The carbazole skeleton is nearly planar [maximum deviation = 0.078 (2) Å], and it is oriented at a dihedral angle of 4.22 (4)° with respect to the adjacent methoxybenzene ring.

Related literature

For the biological activity of carbazole derivatives, see: Knölker & Reddy (2002 ▶). For the use of carbazole derivatives in the syntheses of indole alkaloids, see: Routier et al. (2001 ▶). For the use of benzo[a]carbazoles in cancer treatment, see: Carini et al. (2001 ▶). For the antitumor activity of a series of simple benzo[a]carbazoles against mammary tumors of rats, leukemia, renal tumors, colon cancer and malignant melanoma tumor cell lines, see: von Angerer & Prekajac (1986 ▶); Pindur & Lemster (1997 ▶). For the extensive application of benzo[a]carbazole derivatives as photographic materials, see: Oliveira et al. (2005 ▶. For tetrahydrocarbazole systems present in the frameworks of a number of indole-type alkaloids of biological interest, see: Phillipson & Zenk (1980 ▶); Saxton (1983 ▶); Abraham (1975 ▶). For related structures, see: Hökelek et al. (1994 ▶, 1998 ▶, 1999 ▶, 2004 ▶, 2006 ▶); Patır et al. (1997 ▶); Hökelek & Patır (1999 ▶, 2002 ▶); Çaylak et al. (2007 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₂₁H₂₁NO
M _r = 303.39
Monoclinic,
a = 10.7263 (6) Å
b = 5.5562 (3) Å
c = 13.8967 (7) Å
β = 97.841 (2)°
V = 820.46 (8) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 100 K
0.48 × 0.39 × 0.35 mm

Data collection

Bruker Kappa APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.965, T _max = 0.974
7947 measured reflections
2248 independent reflections
2001 reflections with I > 2σ(I)
R _int = 0.027

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.091
S = 1.04
2248 reflections
270 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810021963/xu2773sup1.cif

e-66-o1634-sup1.cif^{(20.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810021963/xu2773Isup2.hkl

e-66-o1634-Isup2.hkl^{(108.2KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors are indebted to Anadolu University and the Medicinal Plants and Medicine Research Centre of Anadolu University, Eskişehir, Turkey, for the use of the diffractometer.

supplementary crystallographic information

Comment

Carbazole derivatives display a range of biological activities, making them attractive compounds to synthetic and medicinal chemists (Knölker & Reddy, 2002). They also have an important role in the syntheses of indole alkaloids, in which their synthetic derivatives, possessing useful pharmacological properties, are currently under investigation (Routier et al., 2001). Benzo -annulated carbazole ring systems are found only rarely in natural products. The benzo[a]carbazoles, containing an aromatic ring fused to the a-face of the carbazole nucleus, are potential candidates for cancer treatment as a result of DNA intercelative binding properties (Carini et al., 2001). A series of simple benzo[a]carbazoles have been shown to bind to estrogen receptors and inhibit the growth of mammary tumors of rats (Angerer & Prekajac, 1986). Some benzo[a]carbazoles exhibit a pronounced antitumor activity against leukemia, renal tumor, colon cancer, and malignant melanoma tumor cell lines (Pindur & Lemster, 1997). Benzo[a]carbazole derivatives have also found extensive application as photographic materials (Oliveira et al., 2005).

Tetrahydrocarbazole systems are present in the framework of a number of indole-type alkaloids of biological interest (Phillipson & Zenk, 1980; Saxton, 1983; Abraham, 1975). The structures of tricyclic, tetracyclic and pentacyclic ring systems with dithiolane and other substituents of the tetrahydrocarbazole core, have been the subject of much interest in our laboratory. These include 1,2,3,4-tetrahydrocarbazole-1-spiro-2'-[1,3]dithiolane, (II) (Hökelek et al., 1994), N-(2-methoxyethyl)-N-{2,3,4,9-tetrahydrospiro[1H-carbazole-1, 2-(1,3)dithiolane]-4-yl}benzene-sulfonamide, (III) (Patır et al., 1997), spiro[carbazole-1(2H),2'-[1,3]-dithiolan]-4(3H)-one, (IV) (Hökelek et al., 1998), 9-acetonyl-3-ethylidene-1,2,3,4-tetrahydrospiro[carbazole-1,2'-[1,3] dithiolan]-4-one, (V) (Hökelek et al., 1999), N-(2,2-dimethoxyethyl)-N -{9-methoxymethyl-1,2,3,4-tetrahydrospiro[carbazole-1,2'-[1,3]dithiolan] -4-yl}benzamide, (VI) (Hökelek & Patır, 1999), 3a,4,10,10b-tetrahydro-2H -furo[2,3-a]carbazol-5(3H)-one, (VII) (Çaylak et al., 2007); also the pentacyclic compounds 6-ethyl-4-(2-methoxyethyl)-2,6-methano-5-oxo-hexahydro- pyrrolo(2,3 - d)carbazole-1-spiro-2'-(1,3)dithiolane, (VIII) (Hökelek & Patır, 2002), N-(2-benzyloxyethyl)-4,7-dimethyl-6-(1,3-dithiolan-2-yl)-1,2, 3,4,5,6-hexahydro-1,5-methano-2-azocino[4,3-b]indol-2-one, (IX) (Hökelek et al., 2004) and 4-ethyl-6,6-ethylenedithio-2-(2-methoxyethyl)-7-methoxy- methylene-2,3,4,5,6,7-hexahydro-1,5-methano-1H-azocino[4,3-b]indol-3-one, (X) (Hökelek et al., 2006). The title compound, (I), may be considered as a synthetic precursor of tetracyclic indole alkaloids of biological interests. The present study was undertaken to ascertain its crystal structure.

The title compound consists of a carbazole skeleton with a methoxy benzoato group fused to the a-face of the carbazole nucleus, and a butyl group attached to atom N9 (Fig. 1), where the bond lengths (Allen et al., 1987) and angles are within normal ranges, and generally agree with those in compounds (II)-(X). In all structures atom N9 is substituted.

An examination of the deviations from the least-squares planes through individual rings shows that rings A (C1—C4/C4a/C9a), B (C4a/C5a/C8a/N9/C9a), C (C5a/C5—C8/C8a) and D (C7/C8/C14—C17) are planar. The carbazole skeleton, containing the rings A, B and C are also nearly planar [with a maximum deviation of 0.078 (2) Å for atom C2] with dihedral angles of A/B = 2.37 (6), A/C = 5.01 (5) and B/C = 2.81 (5) ° Ring D is oriented with respect to the planar carbazole skeleton at a dihedral angle of 4.22 (4) °. So, it is nearly coplanar with the carbazole skeleton. Atoms O1 and C18 displaced by 0.010 (1) and -0.045 (2) Å from the plane of ring D, respectively, while atom C10 is 0.092 (2) Å away from the plane of the carbazole skeleton.

In the crystal structure, molecules are alongated along the c axis and stacked along the b axis (Fig. 2).

Experimental

For the preparation of the title compound, (I), a solution of 3-methoxy-11H -benzo[a]carbazole (1.00 g, 4.0 mmol) in dichloromethane (20 ml) was cooled to 273 K, and then sodium hydroxide (2 ml, 50%), tetrabutylammonium hydrogen sulfate (0.10 g) and butyl bromide (0.62 g, 4.5 mmol) were added. The mixture was stirred for 1 h at 273 K, and then 2 h at 298 K. It was washed with hydrochloric acid (50 ml, 10%) and the organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was crystallized from methanol (yield; 1.15 g, 93%, m.p. 369 K).