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Synthesis and X-ray diffraction data of 6,8-dimethyl-cis-2-vinyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol and 8-chloro-9-methyl-cis-2-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol

Published online by Cambridge University Press:  05 March 2012

M. A. Macías ,
J. A. Henao ,
Lina María Acosta  and
Alirio Palma
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
Lina María Acosta
Affiliation:
Laboratorio de Síntesis Orgánica (LSO), 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
Alirio Palma
Affiliation:
Laboratorio de Síntesis Orgánica (LSO), 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 6,8-dimethyl-cis-2-vinyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2a) (Chemical formula C14H19NO) and 8-chloro-9-methyl-cis-2-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2b) (Chemical formula C14H18ClNO) were prepared via the reductive cleavage of the bridged N-O bond of the corresponding 1,4-epoxytetrahydro-1-benzazepines. The X-ray powder diffraction patterns for the new compounds were obtained. The compound 2a was found to crystallize in an orthorhombic system with space group Pmn21 (No. 31), refined unit-cell parameters a = 19.422(6) Å, b = 6.512(3) Å, c = 9.757(4) Å and V = 1234.0(5) Å3. The compound 2b was found to crystallize in a monoclinic system with space group P21/m (No. 11), refined unit-cell parameters a = 17.570(4) Å, b = 8.952(3) Å, c = 14.985(4) Å, β = 101.66(2)°, and V = 2308.3(9) Å3.

Keywords

tetrahydro-1-benzazepineX-ray powder diffraction dataantiparasitic agents
Type
New Diffraction Data
Information
Powder Diffraction , Volume 26 , Issue 4 , December 2011 , pp. 346 - 349
Copyright
Copyright © Cambridge University Press 2011

INTRODUCTION

Tetrahydro-1-benzazepine derivatives exhibit a broad spectrum of diverse and important pharmacological properties. For example, different tetrahydro-1-benzazepines have been reported as potent arginine vasopressin antagonists for both V1A and V2 receptors (Matthews et al., Reference Matthews, Greco, Hecker, Hoekstra, Andrade-Gordon, de Garavilla, Demarest, Ericson, Gunnet, Hageman, Look, Moore and Maryanoff2003; Shimada et al., Reference Shimada, Taniguchi, Matsuhisa, Sakamoto, Yatsu and Tanaka2000), and some other derivatives have been reported as potent inhibitors of cyclin dependent kinases (Schultz et al., Reference Schultz, Link, Leost, Zaharevitz, Gussio, Sausville, Meijer and Kunick1999). Other tetrahydro-1-benzazepine derivatives such as paullones exhibited potent activity against parasites of Leishmania mexicana (Knockaert et al., Reference Knockaert, Wieking, Schmitt, Leost, Grant, Mottram, Kunick and Meijer2002) and Trypanosoma cruzi (Zuccotto et al., Reference Zuccotto, Zvelebil, Brun, Chowdhury, Lucrezia, Leal, Maes, Ruiz-Perez, Pacanowska and Gilbert2001), the etiologic agents of the leishmaniasis and Chagas disease, respectively. This broad spectrum of biological activity awakened the interest of the synthetic chemists in this heterocyclic system. In this context, we have developed an efficient synthetic method to obtain new cis-2-aryl-4-hydroxytetrahydro-1-benzazepines starting from ortho-allyl-N-benzylanilines (Gómez et al., Reference Gómez-Ayala, Stashenko, Palma, Bahsas and Amaro-Luis2006). Compounds of this type showed promising activity against T. cruzi and Leishmania chagasi parasites (Palma et al., Reference Palma, Yépes, Leal, Coronado and Escobar2009, Gómez-Ayala et al., Reference Gómez-Ayala, Stashenko, Palma, Bahsas and Amaro-Luis2006, Reference Gómez-Ayala, Castrillón, Palma, Leal, Escobar and Bahsas2010). Additionally, we have also described the stereoselective synthesis of cis-4-hydroxy-2-alkenyltetrahydro-1-benzazepines (Acosta et al. Reference Acosta, Palma and Bahsas2010). In this work, we report the X-ray powder diffraction (XRPD) data of 6,8-dimethyl-cis-2-vinyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2a) and 8-chloro-9-methyl-cis-2-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2b).

EXPERIMENTAL

Synthesis

As shown in Figure 1, the synthesis of the compounds 2a and 2b involves the treatment of a methanolic cooled ice bath solution of the 1,4-epoxy-cycloadducts 1a and 1b with a seven-fold molar excess of glacial acetic acid, ten-fold molar excess of zinc powder, and seven-fold molar excess of hydrochloric acid (37% HCl). The organic crudes were purified by column chromatography on silica gel using heptane/ethyl acetate (compositions ranged from 10:1 to 1:1 v/v) as eluent to give 2a and 2b in 94% and 90% yields, respectively.

Powder data collection

A small portion of the title compounds were gently ground in an agate mortar and sieved to a grain size less than 38 μm. The specimens were mounted on a zero-background specimen holder (Buhrke et al., Reference Buhrke, Jenkins and Smith1998). The XRPD patterns were recorded with a D8 FOCUS BRUKER diffractometer operating in Bragg-Brentano geometry equipped with an X-ray tube (Cu Kα 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. XRPD data were collected at room temperature (298 K).

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 Kα2 component

Figure 1. Synthesis of the cis-2-alkenyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ols 2a,b.

Figure 2. X-ray powder diffraction pattern of 6,8-dimethyl-cis-2-vinyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2a).

(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 diffraction (XRPD) patterns of the compounds 2a and 2b are shown in Figures 2 and 3, respectively. XRPD data for the compounds are given in Tables I and II. The XRPD patterns were successfully indexed using the DICVOL06 program (Boultif and Louër, Reference Boultif and Loüer2006) with an absolute error of 0.03° 2θ. Compounds 2a and 2b were found to be orthorhombic and monoclinic, respectively. The space groups, Pmn21 (No. 31) for 2a and P21/m (No. 11) for 2b, were estimated by the CHEKCELL program (Laugier and Bochu, Reference Laugier and Bochu2002), which were compatible with the

TABLE I. X-ray powder diffraction data of 6,8-dimethyl-cis-2-vinyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2a).

TABLE II. X-ray powder diffraction data of 8-chloro-9-methyl-cis-2-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2b).

TABLE III. Crystal-structure data for 6,8-dimethyl-cis-2-vinyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2a) and 8-chloro-9-methyl-cis-2-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2b).

Figure 3. X-ray powder diffraction pattern of 8-chloro-9-methyl-cis-2-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2b).

systematic absences and with the crystal densities (1.125 g/cm3 for 2a and 1.436 g/cm3 for 2b) in each case. The unit-cell parameters for both compounds were refined with the NBS*AIDS83 program (Miguell et al., Reference Miguell, Hubberd and Stalick1981). Their crystal data, X-ray densities 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 III.

ACKNOWLEDGMENTS

This work was partially supported by COLCIENCIAS (Grant No. 1102-408-20563). The authors would like to acknowledge to Miguel A. Ramos from the Instituto Zuliano de Investigaciones Tecnológicas, INZIT (Maracaibo-Venezuela) for the data collection. M. A. Macías thanks to COLCIENCIAS for his doctoral fellowship.

References

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Figure 0

Figure 1. Synthesis of the cis-2-alkenyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ols 2a,b.

Figure 1

Figure 2. X-ray powder diffraction pattern of 6,8-dimethyl-cis-2-vinyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2a).

Figure 2

TABLE I. X-ray powder diffraction data of 6,8-dimethyl-cis-2-vinyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2a).

Figure 3

TABLE II. X-ray powder diffraction data of 8-chloro-9-methyl-cis-2-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2b).

Figure 4

TABLE III. Crystal-structure data for 6,8-dimethyl-cis-2-vinyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2a) and 8-chloro-9-methyl-cis-2-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2b).

Figure 5

Figure 3. X-ray powder diffraction pattern of 8-chloro-9-methyl-cis-2-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-4-ol (2b).