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Synthesis and X-ray powder diffraction data of cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline

Published online by Cambridge University Press:  10 September 2013

M.A. Macías ,
J.A. Henao ,
Arnold R. Romero Bohórquez  and
Vladimir V. Kouznetsov
M.A. Macías*
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
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: mariomacias@ciencias.uis.edu.co
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Abstract

The 2,4-diaryl 1,2,3,4-tetrahydroquinoline derivative (1), described in the title (Chemical formula: C23H22N2O3), was synthesized via the “one-pot” three-component imino Diels–Alder reaction catalyzed by Cu(OTf)2. Molecular characterization was performed by 1H and 13C NMR, Fourier transform-infrared, and gas chromatography-mass spectrometry. The X-ray powder diffraction pattern for the title compound was analyzed and found to be crystallized in an orthorhombic system with space group P212121 (No. 19) and refined unit-cell parameters a = 8.6415(8) Å, b = 12.679(2) Å, c = 17.601(2) Å, and V = 1928.4(2) Å3.

Keywords

imino Diels–Alder reactiontetrahydroquinolinethree-component reactionX-ray powder diffraction
Type
New Diffraction Data
Information
Powder Diffraction , Volume 28 , Issue 4 , December 2013 , pp. 307 - 311
Copyright
Copyright © International Centre for Diffraction Data 2013 

I. INTRODUCTION

Heterocyclic systems with quinoline and tetrahydroquinoline nucleus are known as a remarkable class of natural and synthetic compounds, being privileged moieties in medicinal chemistry. Many pharmaceutical agents and different natural products with significant biological activity are built on the (tetrahydro)quinoline scaffolds (Katritzky et al., Reference Katritzky, Rachwal and Rachwal1996; Kouznetsov et al., Reference Kouznetsov, Palma, Ewert and Varlamov1998). A large number of reports showed that these compounds display a wide spectrum of biological activities, including antimalarial activity (Bendale et al., Reference Bendale, Olepu, Kumar, Buldule, Rivas, Nallan, Smart, Yokoyama, Ankala, Pendyala, Floyd, Lombardo, Williams, Buckner, Chakrabarti, Verlinde, Van Voorhis and Gelb2007), estrogenic receptor (Wallace et al., Reference Wallace, Lauwers, Jones and Dodge2003; Chen, et al., Reference Chen, Lin, Ning, Yang, Yan, Xie, Shen and Wang2007), anti-inflammatory behavior (Calhoun et al. Reference Calhoun, Carlson, Crossley, Datko, Dietrich, Heatherington, Marshall, Meade, Opalko and Shepherd1995), among others.

In accordance with the importance of the compounds possessing these skeletons, there is a large list of methods developed for their synthesis (Sridharan et al., Reference Sridharan, Suryavanshi and Menéndez2011). Among them, the cycloaddition reactions stand out as powerful reactions to construct rapidly the tetrahydroquinoline systems. The Lewis acid-catalyzed imino Diels–Alder reaction between aldimines and electron-rich alkenes or its three-component version is probably the most powerful and successful synthetic tool to construct rapidly N-containing six-membered heterocyclic compounds, including tetrahydroquinolines (Buonora, et al., Reference Buonora, Olsen and Oh2001; Glushkov and Tolstikov, Reference Glushkov and Tolstikov2008; Kouznetsov, Reference Kouznetsov2009). Recently, interesting chemical transformation with phenylpropenoid derivatives (electron-rich alkenes, e.g. trans-anethole) as dienophiles in this cycloaddition process for obtaining 2,4-diaryl 1,2,3,4-tetrahydroquinoline derivatives under green conditions was reported by our laboratory (Kouznetsov et al., Reference Kouznetsov, Romero Bohórquez and Stashenko2007; Kouznetsov et al., Reference Kouznetsov, Merchan and Romero2008) and others (He et al., Reference He, Bekkaye, Retailleau and Masson2012). In this regard, our ongoing research program focused on the chemistry of the bioactive tetrahydroquinoline derivatives with anethole fragments (Romero et al., Reference Romero Bohórquez, Escobar, Leal and Kouznetsov2012). In this work, we report the X-ray powder diffraction (XRPD) data of the compound cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline (1) prepared using a commercial trans-anethole as a dienophile in the “one-pot” three-component imino Diels–Alder reaction (Povarov reaction) catalyzed by the Lewis acid Cu(OTf)2 and starting from the corresponding 4-nitroaniline and benzaldehyde (Romero et al., Reference Romero Bohórquez, Kouznetsov and Doyle2011).

II. EXPERIMENTAL

A. Synthesis

As shown in Figure 1, the title compound was synthesized according to the following experimental procedure: a mixture of 4-nitroaniline (2.90 mmol) and benzaldehyde (3.19 mmol) in anhydrous CH3CN (15 ml) was stirred at room temperature for 30 min. Then, Cu(OTf)2 (0.29 mmol) was added in solution into the mixture. Over a period of 30 min, a solution of commercial trans-anethole (3.48 mmol) in CH3CN (10 ml) was added dropwise. The resulting mixture was stirred at room temperature for 16 h (overnight). After completion of the reaction as indicated by TLC, the reaction mixture was diluted with water (30 ml) and extracted with ethyl acetate (3 times × 15 ml). The organic layer was separated and dried (Na2SO4), concentrated under vacuum and the crude product was purified by column chromatography using silica gel (between 60 and 120 mesh) and eluted with petroleum ether–ethyl acetate to afford pure title tetrahydroquinoline (1) (yield 98%). This compound was obtained as yellow solid with melting point between 203 and 204 °C (uncorrected) recrystallizing by slow evaporation in dichloromethane solution.

Figure 1. Synthesis of cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline (1) via “one pot” three-component imino Diels–Alder reaction.

Its structural characterization was achieved by the use of Fourier transform-infrared spectroscopy (FT-IR) and mass spectrometry with electron impact (MS-EI). Analysis revealed the following characteristic absorption bands 3448, 3339, 1610, 1495, and 1305 cm−1 (FT-IR) and a molecular peak m/z: = 374 (15, M +•) (MS-EI). In addition, nuclear magnetic resonance on protons (1H NMR) (400 MHz, CDCl3 Me4Si) and nuclear magnetic resonance on carbons (13C-NMR) (100 Hz, CDCl3 Me4Si), were performed to confirm the molecular structure of the title compound. Proton spectrum revealed the following data: δ (ppm), 0.58 (3H, d, J = 6.5 Hz, –CH3), 2.15 (1H, m, 3-H), 3.70 (1H, d, J = 11.2 Hz, 2-H), 3.83 (3H, s, Ar-OCH3), 4.23 (1H, d, J = 10.0 Hz, 4-H), 4.87 (1H, s, NH), 6.44 (1H, d, J = 8.9 Hz, 8-H), 6.90 (2H, d, J = 8.6 Hz, 2′-HAr), 7.11 (2H, d, J = 8.6 Hz, 3′-HAr), 7.35–7.40 (5H, m, all-HAr), 7.48 (1H, br s, 5-H), and 7.90 (1H, dd, J = 8.9, 2.4 Hz, 7-H). Similarly, its carbon spectrum offered the following data: δ (ppm), 158.7, 150.2, 141.2, 138.0, 133.8, 130.1, 128.9, 128.5, 127.7, 126.6, 124.8, 124.2, 114.4, 112.2, 63.6, 55.2, 50.6, 40.1, and 16.2. In this way, both spectroscopy methods established the tetrahydroquinoline structure of the title compound.

B. Powder data collection

A small amount of the compound C23H22N2O3 was gently ground in an agate mortar and sieved to a grain size of less than 38 μm. The specimen was mounted on a zero-background specimen holder (Buhrke et al., Reference Buhrke, Jenkins and Smith1998) for the respective measurement. The XRPD data were collected at 295 K with D8 FOCUS BRUKER diffractometer operating in Bragg-Brentano geometry equipped with a Cu-target X-ray tube (40 kV and 40 mA), a nickel filter, and an one-dimensional LynxEye detector. A fixed antiscatter slit of 8 mm, receiving slit of 1 mm, soller slits of 2.5°, and a detector slit of 3 mm were used. The scan range was from 2 to 70° 2θ with a step size of 0.02° 2θ and a counting time of 0.4 s per step.

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

III. RESULTS AND DISCUSSION

The XRPD pattern of cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline is shown in Figure 2 and the data for this compound are given in Table I. The XRPD pattern was successfully indexed using the DICVOL06 program (Boultif and Louër, Reference Boultif and Louër2006) on an orthorhombic cell with an absolute error of ±0.03°2θ in the calculations. The space group, P212121 (No. 19), was estimated by the CHEKCELL program (Laugier and Bochu, Reference Laugier and Bochu2002) that was compatible with the systematic absences and with the crystal density, 1.288 g/cm3. The unit-cell parameters were refined with the NBS*AIDS83 program (Mighell et al., Reference Miguell, Hubberd and Stalick1981). The crystal data, X-ray density as well as 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.

Figure 2. X-ray powder diffraction pattern of cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline (1).

Table I. X-ray powder diffraction data of cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline (1). CuKα 1 radiation (λ = 1.5406 Å).

Table II. Crystal-structure data for cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline (1).

ACKNOWLEDGEMENTS

The authors are grateful for financial support by the Universidad Industrial de Santander (VIE-UIS, project 5714). ARRB acknowledges COLCIENCIAS for the fellowship for the PhD studies (2005–2010). M.A.M. acknowledges COLCIENCIAS for the doctoral fellowship.

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Figure 0

Figure 1. Synthesis of cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline (1) via “one pot” three-component imino Diels–Alder reaction.

Figure 1

Figure 2. X-ray powder diffraction pattern of cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline (1).

Figure 2

Table I. X-ray powder diffraction data of cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline (1). CuKα1 radiation (λ = 1.5406 Å).

Figure 3

Table II. Crystal-structure data for cis-4-(4-methoxyphenyl)-3-methyl-6-nitro-2-phenyl-1,2,3,4-tetrahydroquinoline (1).