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Synthesis and X-ray diffraction data of 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline

Published online by Cambridge University Press:  10 October 2013

H.A. Camargo ,
A. Sánchez ,
J.A. Henao ,
Arnold R. Romero Bohórquez  and
Vladimir V. Kouznetsov
H.A. Camargo
Affiliation:
Grupo de Investigación en Nuevos Materiales y Energías Alternativas (GINMEA), Facultad de Química Ambiental, Universidad Santo Tomás, Campus Universitario Floridablanca, Santander, Colombia
A. Sánchez
Affiliation:
Grupo de Investigación en Nuevos Materiales y Energías Alternativas (GINMEA), Facultad de Química Ambiental, Universidad Santo Tomás, Campus Universitario Floridablanca, Santander, Colombia
J.A. Henao*
Affiliation:
Grupo de Investigación en Química Estructural (GIQUE), Escuela de Química, Facultad de Ciencias, Universidad Industrial de Santander, A.A. 678, Carrera 27, Calle 9 Ciudadela Universitaria. Bucaramanga, Colombia
Arnold R. Romero Bohórquez
Affiliation:
Laboratorio de Química Orgánica y Biomolecular (LQOBio), Escuela de Química, Facultad de Ciencias, Universidad Industrial de Santander, A.A. 678, Carrera 27, Calle 9 Ciudadela Universitaria. Bucaramanga, Colombia
Vladimir V. Kouznetsov
Affiliation:
Laboratorio de Química Orgánica y Biomolecular (LQOBio), Escuela de Química, Facultad de Ciencias, Universidad Industrial de Santander, A.A. 678, Carrera 27, Calle 9 Ciudadela Universitaria. Bucaramanga, Colombia
*
a) Author to whom correspondence should be addressed. Electronic mail: jahenao@uis.edu.co
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Abstract

The compound 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2) (chemical formula C23H22N2) was synthesized through the free-solvent oxidation reaction mediated by elemental sulfur from the corresponding 2-ethyl-6-(pyridin-4-yl)-5,6,6a,11b-tetrahidro-7H-indeno[2,1-c]quinoline (1), an adduct easily obtained, using the Lewis acid-promoted [4 + 2] cycloaddition reaction. Preliminary molecular characterization was performed by Fourier transform-infrared and gas chromatography-mass spectrometry. The X-ray powder diffraction (XRPD) pattern for the title compound was analyzed and found to be crystallized in monoclinic system, space group P21/n (N° 14) with refined unit-cell parameters a = 20.795 (8) Å, b = 7.484 (2) Å, c = 10.787 (2) Å and ß = 93.96° (2). The volume of the unit cell is V = 1674.8 (6) Å3.

Keywords

indeno[2, 1-c]quinolinesantitumoral activityX-ray powder diffraction
Type
New Diffraction Data
Information
Powder Diffraction , Volume 29 , Issue 1 , March 2014 , pp. 53 - 57
Copyright
Copyright © International Centre for Diffraction Data 2013 

I. INTRODUCTION

Quinoline derivatives are important natural and synthetic compounds with remarkable and diverse pharmacological properties (Kouznetsov et al., 2005). Within the quinoline family, tetracyclic and pseudo-planar compounds with antitumoral activity as topoisomerases (topo) inhibitors are the more biological relevant examples (Gelderblom and Sparreboom, Reference Gelderblom, Sparreboom, Pinedo and Smorenburg2006).

Since the discovery of camptothecin, a natural topoisomerase (topo I) inhibitor (Priel et al., Reference Priel, Showalter, Roberts, Oroszlan and Blair1991; Pommier, Reference Pommier2006), a constant search for new compounds with the ability to inhibit the topoisomerases I/II enzymes has been undertaken (Li et al., Reference Li, Zu, Shi and Yao2006). The most relevant indenoquinoline compound because of its potent cytotoxicity against different leukemia lines (Ohyama et al., Reference Ohyama, Li, Utsugi, Irie, Yamada and Sato1999; Twelves et al., Reference Twelves, Gardner, Flavin, Sludden, Dennis, de Bono, Beale, Vasey, Hutchison, Macham, Rodríguez, Judson and Bleehen1999) is the 6-{[2(dimethylamino)ethyl]amino}-3-hydroxy-7H-indeno[2,1-c]quinolin-7-one, known as TAS-103. The exhibited anti-cancer activity is because of its ability to function as a dual inhibitor of both topo I/II, and it has been investigated in clinical studies (Ewesuedo et al., Reference Ewesuedo, Iyer, Das, Koenig, Mani, Vogelzang, Schilsky, Brenckman and Ratain2001; Ishida and Asao, Reference Ishida and Asao2002).

In our preliminary studies of TAS-103 analogs, we have reported a work where the diastereoselective synthesis of corresponding 6-pyridinyl-(tetrahydro)indeno[2,1-c]quinolines based on the Lewis acid-catalyzed imino Diels–Alder reaction (Kouznetsov et al., Reference Kouznetsov, Romero Bohórquez and Astudillo2009) was described and their biological activity was studied. It was found that these compounds were active against MCF-7, H-460, and SF-268 cancer cell lines making them potential anti-cancer agents (Kouznetsov et al., Reference Kouznetsov, Ochoa Puentes, Romero Bohorquez, Zacchino, Sortino, Gupta, Vásquez and Bahsas2006). However, the information about the crystallographic study by X-ray diffraction of this type of derivatives has been little explored.

In this regard, our ongoing research program focused on the chemistry of the anti-tumoral bioactive (tetrahydro)indeno[2,1-c]quinoline derivatives and its X-ray crystallographic study. Here, we discuss a simple methodology for preparation of compound 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2) through the free-solvent oxidation reaction mediated by elemental sulfur from the corresponding 2-ethyl-6-(pyridin-4-yl)-5,6,6a,11b-tetrahidro-7H-indeno[2,1-c]quinoline (1) (Kouznetsov et al., Reference Kouznetsov, Ochoa Puentes, Romero Bohorquez, Zacchino, Sortino, Gupta, Vásquez and Bahsas2006) and report the results of the molecular characterization (FT-IR, GC-MS) and X-ray powder diffraction (XRPD) data.

II. EXPERIMENTAL

A. Synthesis

As shown in Figure 1, the compound C23H22N2 was synthesized according to the following experimental procedure: A homogenate mixture of 2-ethyl-6-(pyridin-4-yl)-5,6,6a,11b-tetrahydro-7H-indeno[2,1-c]quinoline (1) (0.5 mmol) and elemental sulfur (1.5 mmol) was melted at 210–215 °C for 10 min. After completion of the reaction indicated by the complete liberation of H2S (g), the reaction mixture was directly purified by column chromatography using alumina and eluted with petroleum ether-ethyl acetate to obtain 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2) as white pale-yellow crystals with 82% yield. The purified compound was recrystallized by slow evaporation in methanol solution. The melting point (uncorrected) was between 162 and 164 °C and the density was 1.268 g cm−3, which was measured by the flotation method in an aqueous solution of potassium iodine.

Figure 1. Synthesis of 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2).

Its structural characterization was carried out by Fourier transform-infrared spectroscopy (FT-IR) and mass spectrometry with electron impact (MS-EI). Analysis of FT-IR revealed the following characteristic absorption bands (υ, cm−1) 2968 (C-H); 1591 (C = C); 1541 (C = C) and 1375 (C-H), while MS-EI analysis showed the characteristic molecular peak m/z = 326 (M +•).

B. Powder data collection

A small portion of the compound C23H22N2 was gently ground in an agate mortar and sieved to a grain size of less than 38 μm. The specimen was mounted on a polymethyl methacrylate (PMMA) specimen holder. The XRPD pattern was recorded with a D8 Advance Bruker diffractometer operating in DaVinci geometry equipped with a Cu-target X-ray tube (40 kV and 30 mA) using a nickel filter and a 1-dimensional LynxEye detector. A receiving slit (RS) of 0.6 mm and primary and secondary soller slits (SS) of 2.5° were used. The scan range was 2–70° 2θ with a step size of 0.015 26° and a count time of 2 s per step. XRPD data were collected at room temperature (25 °C).

PowderX program (Dong, Reference Dong1999) was used to remove the background (Sonneveld and Visser, Reference Sonneveld and Visser1975), smoothing (Saviztky and Golay, Reference Saviztky and Golay1964), to eliminate the CuKα 2 component (Rachinger, Reference Rachinger1948) and the second derivative method was used to determine the position and intensities of the diffraction peaks.

III. RESULTS AND DISCUSSION

The X-ray powder diffraction data for the compound (2) are given in the Table I. All reflections were indexed successfully using the DICVOL06 program (Boultif and Louër, Reference Boultif and Loüer2004) on a monoclinic system unit cell and the peak positions, each with an absolute error of 0.03° (2θ), were used in the calculations. The CHEKCELL program (Laugier and Bochu, Reference Laugier and Bochu2002) was used to estimate the space group, P21 /n (No. 14), which was compatible with the systematic absences and with the crystal density. The unit-cell parameters of the compound (2) were refined with the program NBS*AIDS83 software (Miguell et al., Reference Miguell, Hubberd and Stalick1981). Its crystal data, X-ray density, and figures of merit M 20 (de Wolff, Reference de Wolff1968) and F 20 (Smith and Snyder, Reference Smith and Snyder1979) are compiled in Table II. The X-ray powder pattern of the compound 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2) is shown in Figure 2.

Figure 2. Powder X-ray diffraction pattern of 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2).

Table I. X-ray powder diffraction data of 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2).

aCuKα1 with λ = 1.5406 Å.

Table II. Parameters obtained by X-ray powder diffraction for the compound 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2).

ACKNOWLEDGEMENTS

H. A. Camargo thanks Universidad Santo Tomás (Bucaramanga-Colombia) for their support with the project which was approved in the VII internal call of research projects. A. R. R. Bohórquez is grateful for the financial support by the Universidad Industrial de Santander (VIE-UIS, project 5714) and COLCIENCIAS for support in the PhD studies (2005–2010).

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Figure 0

Figure 1. Synthesis of 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2).

Figure 1

Figure 2. Powder X-ray diffraction pattern of 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2).

Figure 2

Table I. X-ray powder diffraction data of 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2).

Figure 3

Table II. Parameters obtained by X-ray powder diffraction for the compound 2-ethyl-6-(pyridin-4-yl)-7H-indeno[2,1-c]quinoline (2).