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Synthesis and X-ray diffraction data of 1-[N-(methyl)-(3,5-dimethylphenylamino)]methylnaphthalene

Published online by Cambridge University Press:  05 March 2012

H. A. Camargo ,
N. M. Habran ,
J. A. Henao ,
D. F. Amado  and
V. V. Kouznetsov
H. A. Camargo
Affiliation:
Grupo de Investigación en Química Estructural (GIQUE), 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
N. M. Habran
Affiliation:
Grupo de Investigación en Química Estructural (GIQUE), 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
J. A. Henao*
Affiliation:
Grupo de Investigación en Química Estructural (GIQUE), 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
D. F. Amado
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
V. 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)Author to whom correspondence should be addressed. Electronic mail: jahenao@uis.edu.co
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Abstract

The 1-[N-(methyl)-(3,5-dimethylphenylamino)]methylnaphthalene (chemical formula C20H21N) was prepared by means of a condensation between alpha-naphthylaldehyde and 3,5-dimethylaniline in anhydrous ethanol to obtain the aldimine (1) which was reduced with NaBH4 to afford the 1-[N-(3,5-dimethylphenylamino)]methylnaphtalene (2), and finally, the compound (3) was obtained by N-alkylation reaction of (2) with methyl iodine (CH3I) and potassium carbonate (K2CO3) in acetone. Final compound (3) was purified by chromatographic column. The XRPD pattern for the new compound, 1-[N-(methyl)-(3,5-dimethylphenylamino)]methylnaphthalene, was obtained. This compound crystallizes in monoclinic system with space group P21/a (No. 14) and refined unit-cell parameters a=13.260(4) Å, b=15.495(5) Å, c=7.719(5) Å, β=90.19(6), and V=1586(1) Å3.

Keywords

aminesX-ray powder diffractionantifungal agents
Type
New Diffraction Data
Information
Powder Diffraction , Volume 26 , Issue 1 , March 2011 , pp. 74 - 77
Copyright
Copyright © Cambridge University Press 2011

INTRODUCTION

The increased use of antifungal and antibacterial agents in recent years has resulted in the development of resistance to these drugs. Resistance to antifungal agents has serious implications for morbidity, mortality, and health care costs in the medical procedures, as well as in the community. Hence, substantial attention has been focused on developing a more detailed understanding of the mechanisms of resistance, improved methods to detect resistance when it occurs, new options for the treatment of infections caused by resistant organisms, and methods to prevent the resistance in the first place (Ghannoum and Rice, Reference Ghannoum and Rice1999). Allylamines, such as terbinafine and naftifina, are good options in the treatment of the diseases caused by fungus (Schäfer-Korting et al., Reference Schäfer-Korting, Schoellmann and Korting2008). Both compounds have been developed as a new class of ergosterol biosynthetic inhibitors that are functionally as well as chemically distinct from the other major classes of ergosterol-inhibiting antifungal agents (Ryder et al., Reference Ryder, Wagner and Leitner1998). Also, the amines are widely used throughout the chemical industry as basic intermediates to prepare fine chemicals, pharmaceuticals, and agrochemicals, including antifungal agent (Kouznetsov et al., Reference Kouznetsov, Vargas, Sortino, Vásquez, Gupta, Freile, Enriz and Zacchino2008; Vargas M. et al., Reference Vargas M., Castelli, Kouznetsov, Urbina, López, Sortino, Enriz, Ribas and Zacchino2003). It is for this reason that is of great interest to carry out the synthesis and molecular and crystallographic characterization of the title compound.

In this work we report synthesis and results on the molecular characterization [FTIR, GC- mass spectrometry (MS), and NMR] and X-ray powder diffraction data for the compound 1-[N-(methyl)-(3,5-dimethylphenylamino)] methylnaphthalene.

TABLE I. X-ray powder diffraction data of 1-[N-(methyl)-(3,5-dimethylphenylamino)] methylnaphthalene.

Figure 1. Synthesis of 1-[N-(methyl)-(3,5-dimethylphenylamino)]methylnaphthalene.

Figure 2. Powder X-ray diffraction pattern of 1-[N-(methyl)-(3,5-dimethylphenylamino)] methylnaphthalene.

EXPERIMENTAL

Synthesis

The title compound was synthesized by means of a condensation in which alpha-naphthylaldehyde (128 mmol) and 3,5-dimethylaniline (128 mmol) in anhydrous ethanol were used to obtain the aldimine (1), whose reduction with NaBH4 (384 mmol) produced the 1-[N-(3,5-dimethylphenylamino)] methylnaphtalene (2) (124 mmol) in excellent yield (96.8%). Finally, the compound (3) was prepared by N-alkylation reaction of the compound (2) (124 mmol) with methyl iodine (CH3I) (372 mmol) in the presence of potassium carbonate (K2CO3) (248 mmol) in anhydrous acetone (40 ml). Final compound (3) was purified by chromatographic column in a yield of 78.9%. Its synthesis is shown in Figure 1. The melting point was between 70 and 72 °C, and density of 1.165 g/cm3, which was taken by the flotation method in an aqueous solution of potassium iodine.

The molecular characterization that was carried out with

TABLE II. Crystal-structure data for 1-[N-(methyl)-(3,5-dimethylphenylamino)]methylnaphthalene.

infrared (IR) spectrometry showed stretching vibrations: =C—HAr (3047.03 cm−1), C—C (1596 cm−1), C—N (1195.67 cm−1), and CH3 (2915.89 cm−1) and bending vibrations: aromatic overtones (2000 to 1650 cm−1), CH3 (1365.38 cm−1), and =C—H (732.83 cm−1); MS gave a molecular peak m/z=275 (M +) (C20H21N); nuclear magnetic resonance on protons (1H NMR, 400 MHz, CDCl3) showed δ to be 8.07 to 8.00 (m, 1H), 7.98 to 7.91 (m, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.62 to 7.52 (m, 2H), 7.44 (t, J=7.6 Hz, 1H), 7.37 (d, J=7.0 Hz, 1H), 6.47 (s, 3H), 4.99 (s, 2H), 3.08 (s, 3H), and 2.30 (s, 6H); and nuclear magnetic resonance on carbons (13C NMR, 101 MHz, CDCl3) presents the following data: δ 150.23 (s), 138.95 (s), 133.99 (s), 133.66 (s), 131.42 (s), 128.98 (s), 127.50 (s), 126.14 (s), 125.80 (d, J=5.0 Hz), 124.16 (s), 122.95 (s), 118.85 (s), 110.30 (s), 54.72 (s), 38.47 (s), and 21.92 (s).

Powder data collection

A small portion of the title compound was gently ground in an agata 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). The XRPD pattern was recorded with a D8 FOCUS BRUKER diffractometer operating in Bragg-Brentano geometry equipped with an X-ray tube (Cu K α 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 count time of 0.4 s/step. Powder data were collected at room temperature (298 K).

Powder analytical software was used to remove the background (Sonneveld and Visser, Reference Sonneveld and Visser1975), smoothing (Saviztky and Golay, Reference Saviztky and Golay1964), to eliminate the K α 2 component (Rachinger, Reference Rachinger1948) and the second derivative method was used to determine the peak positions and intensities of the diffraction peaks.

RESULTS AND DISCUSSION

The X-ray powder pattern of the compound 1-[N-(methyl)-(3,5-dimethylphenylamino)]methylnaphthalene (3) is shown in Figure 2. X-ray powder diffraction data for the compound (3) are given in Table I. All reflections were indexed successfully using the DICVOL06 program (Boultif and Loüer, Reference Boultif and Loüer2004) on a monoclinic unit cell and the peak positions, each with an error of ±0.03° 2θ, were used in the calculations. The space group P21/a (No. 14), estimated by the program CHEKCELL (Laugier and Bochu, Reference Laugier and Bochu2002), was compatible with the systematic absences and with the crystal density. The lattice parameters of the compound (3) 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.

ACKNOWLEDGMENTS

This work was supported by COLCIENCIAS (Grant No. 1102-05-17590). The authors would like to thank Instituto Zuliano de Investigaciones Científicas, INZIT (Maracaibo-Venezuela) for data collection. One of the authors (H.A.C.) thanks Universidad Industrial de Santander for the maintenance scholarship.

References

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Figure 0

TABLE I. X-ray powder diffraction data of 1-[N-(methyl)-(3,5-dimethylphenylamino)] methylnaphthalene.

Figure 1

Figure 1. Synthesis of 1-[N-(methyl)-(3,5-dimethylphenylamino)]methylnaphthalene.

Figure 2

Figure 2. Powder X-ray diffraction pattern of 1-[N-(methyl)-(3,5-dimethylphenylamino)] methylnaphthalene.

Figure 3

TABLE II. Crystal-structure data for 1-[N-(methyl)-(3,5-dimethylphenylamino)]methylnaphthalene.