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Synthesis and X-ray powder diffraction data of N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline

Published online by Cambridge University Press:  30 November 2012

J. A. Pinilla ,
J. A. Henao ,
M. A. Macías ,
Arnold R. Romero Bohórquez  and
Vladimir V. Kouznetsov
J. A. Pinilla
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
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
Arnold R. Romero Bohórquez
Affiliation:
Laboratorio de Química Orgánica y Biomolecular (LQOBio), Centro de Investigación en Biomoléculas, (CIBIMOL), 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), Centro de Investigación en Biomoléculas, (CIBIMOL), Escuela de Química, Facultad de Ciencias, Universidad Industrial de Santander, A.A. 678, Carrera 27, Calle 9 Ciudadela Universitaria, Bucaramanga, Colombia
*
a)To whom correspondence should be addressed. Electronic mail: jahenao@uis.edu.co
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Abstract

The N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline derivative (chemical formula: C24H24ClNO) was obtained from cationic imino Diels–Alder reaction catalyzed by BF3.OEt2. Molecular characterization was performed by 1H and 13C NMR, Fourier transform-infrared and gas chromatography-mass spectrometry. The X-ray powder diffraction (XRPD) pattern for the new compound was analyzed and found to be crystallized in an orthorhombic system with space group Fdd2 (No. 43) and refined unit-cell parameters a = 33.053(7) Å, b = 41.558(9) Å, c = 5.841(1) Å and V = 8023(2) Å3.

Keywords

cationic imino Diels–Alder reactionphenylpropenestetrahydroquinolineX-ray powder diffraction data
Type
New Diffraction Data
Information
Powder Diffraction , Volume 27 , Issue 4 , December 2012 , pp. 269 - 272
Copyright
Copyright © International Centre for Diffraction Data 2012

I. INTRODUCTION

Tetrahydroquinoline derivatives are an important class of natural and synthetic compounds that have shown a wide range of pharmacological activities, among which worth highlighting are their antimalarial and antitumor activities (Jacquemond-Collet et al., Reference Jacquemond-Collet, Benoit-Vical, Mustofa, Stanislas, Mallié and Fourasté2002; Wallace et al., Reference Wallace, Lauwers, Jones and Dodge2003). In the literature, different methods for the synthesis of tetrahydroquinoline derivatives have been reported (Katritzky et al., Reference Katritzky, Rachwal and Rachwal1996; Kouznetsov et al., Reference Kouznetsov, Palma, Ewert and Varlamov1998; Buonora et al., Reference Buonora, Olsen and Oh2001). However, the synthesis of these compounds with substitution in positions C-3 and C-4 and without substitution in position C-2 is rare and often the conditions for carrying out the reactions are drastic or require the use of expensive reagents (Kim et al., Reference Kim, Shin, Beak and Park2006). The imino Diels–Alder reaction between aldimines and alkenes is probably the more effective synthetic tool for the construction of tetrahydroquinoline compounds (Kyselov et al., Reference Kyselov, Smith and Armstrong1998; Crousse et al., Reference Crousse, Bèguè and Bonner-Delpon2000). This method allows the generation of quinoline derivatives with several degrees of structural diversity, thus recently multi-component imino Diels–Alder reactions have gained popularity (Glushkov and Tolstikov, Reference Glushkov and Tolstikov2008; Kouznetsov, Reference Kouznetsov2009). On the one hand, the cationic imino Diels–Alder [4+ + 2]-cycloaddition reaction is shown as a quick and simple method for the synthesis of C4-aryl and C3-methyl tetrahydroquinolines (Beifuss and Ledderhose, Reference Beifuss and Ledderhose1995; Chen and Quian, Reference Chen and Quian2002). On the other hand, phenylpropenoide derivatives (e.g. trans-anethole) are not commonly used as dienophiles in this reaction, although these compounds are “renewable” precursors of easy access (Kouznetsov et al., Reference Kouznetsov, Romero Bohórquez and Stashenko2007, Reference Kouznetsov, Merchan Arenas and Romero Bohórquez2008). There are several examples described in the literature, which demonstrated the high synthetic potential of cationic imino Diels–Alder reaction and even the different compounds obtained are proposed as interesting pharmacological models (Dehnhardt et al., Reference Dehnhardt, Espinal and Venkatesan2008; Kouznetsov and Romero, Reference Kouznetsov and Romero Bohórquez2010). In this work, we report the X-ray powder diffraction (XRPD) data of the new compound N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline prepared using trans-anethole as a dienophile in the cationic imino Diels–Alder reaction (Kouznetsov and Romero, Reference Kouznetsov and Romero Bohórquez2010).

II. EXPERIMENTAL

A. Synthesis

As shown in Figure 1, the synthesis of the compound N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline was performed by mixing N-benzyl-4-chloroaniline (1) (1 mmol) with formaldehyde (37% in MeOH, 1.1 mmol) in MeCN (10 ml), the mixture was stirred for 10 min at room temperature to give rise to the cationic intermediate (2). Later, without isolating the intermediate and at 0 °C BF3.OEt2 was added dropwise (1.1 mmol). After 30 min, the dienophile reactant (trans-anethole, 1.1 mmol) was added to the mixture for about 5 min. The resulting mixture was stirred at 70 °C for 8 h. After completion of the reaction as indicated by thin layer chromatography, the reaction mixture was obtained with EtOAc (3 × 15 ml). The organic layer was separated, dried with sodium sulfate (Na2SO4), and concentrated under vacuum. The crude product was purified by column chromatography using silica gel (60 mesh) and petroleum ether-ethyl acetate as eluents to enter the compound under study (3) as white crystals with a yield of 76%. The melting point was between 125 and 127 °C, and the density was 1.245 g cm−3, which was measured by the flotation method using an aqueous solution of potassium iodine.

Figure 1. Synthesis of N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline.

Molecular characterization was carried out by analysis of the main absorption bands observed in the infrared spectrum (Fourier transform-infrared): 2950, 1640, 1601 and 1501 cm−1; nuclear magnetic resonance (NMR) on protons 1H NMR (400 MHz, CDCl3, Me4Si) showed δ (ppm): 0.91 (d, J = 6.6 Hz, 3H, 3-CH3), 2.20 (m, 3H, H-3), 3.10 (dd, J = 11.5, 8.1 Hz, 1H, H-2ax), 3.30 (dd, J = 11.6, 3.7 Hz, 1H, H-2eq), 3.60 (d, J = 8.0 Hz, 1H, H-4), 3.81 (s, 3H, 4′-OCH3), 4.50 (s, 2H, N-CH2Ph), 6.46 (d, J = 8.8 Hz, 1H, H-8), 6.63 (br. s, 1H, H-5), 6.85 (d, J = 8.4 Hz, 2H, 2′-ArH), 6.91 (dd, J = 7.7, 2.1 Hz, 1H, H-7), 7.01 (d, J = 8.4 Hz, 2H, 3′-ArH), 7.24–7.35 (m, 5H, Ph-H); NMR on carbons 13C NMR (100 Hz, CDCl3, Me4Si) present the following data δ (ppm): 158.2, 143.9, 138.4, 136.7, 129.9, 129.8, 128.7, 127.0, 127.0, 126.5, 126.2, 120.6, 113.9, 112.0, 55.4, 55.2, 54.6, 50.6, 34.3 and 18.2; and mass spectrometry with electron impact (MS-EI) gave a molecular peak m/z: 377 (60, M +) (C24H24ClNO), 254 (36), 178 (39), 121 (29) and 91 (100).

B. Powder data collection

A small amount of the compound C24H24ClNO 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 a D8 FOCUS BRUKER diffractometer operating in Bragg–Brentano geometry equipped with an X-ray tube (CuKα radiation: λ = 1.5406 Å, 40 kV and 40 mA) using a nickel filter and a 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 Savitzky 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 N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-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 Loüer2006) on an orthorhombic cell with an absolute error of ±0.03°2θ in the calculations. The space group, Fdd2 (No. 43) was estimated by the CHEKCELL program (Laugier and Bochu, Reference Laugier and Bochu2002), which was compatible with the systematic absences and with the crystal density, 1.245 g cm−3. The unit-cell parameters were refined with the NBS*AIDS83 program (Mighell et al., Reference Mighell, Hubbard 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. XRPD pattern of N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline.

TABLE I. XRPD data of N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline.

TABLE II. Crystal-structure data for N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline.

ACKNOWLEDGEMENTS

This work was supported by grant RC-245-2011 Colciencias (Patrimonio Autónomo del Fondo Nacional de Financiamiento para la Ciencia, la Tecnología y la Innovación, Francisco José de Caldas). The authors would like to acknowledge Miguel A. Ramos from Instituto Zuliano de Investigaciones Tecnológicas, INZIT (Maracaibo-Venezuela) for data collection. A.R.R.B thanks Colciencias for his doctoral fellowship (2005–2010). M.A.M. thanks Colciencias for his doctoral fellowship.

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Figure 0

Figure 1. Synthesis of N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline.

Figure 1

Figure 2. XRPD pattern of N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline.

Figure 2

TABLE I. XRPD data of N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline.

Figure 3

TABLE II. Crystal-structure data for N-benzyl-6-chloro-4-(4-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline.