I. INTRODUCTION
Previously, we have described a simple and efficient synthetic pathway to obtain a wide range of new substituted 1,4-epoxy-2,3,4,5-tetrahydro-1-benzazepines and their reduced 2,3,4,5-tetrahydrobenzo[b]azepin-4-ols starting from appropriate N-substituted ortho-allylanilines (Gómez-Ayala et al., Reference Gómez-Ayala, Stashenko, Palma, Bahsas and Amaro-Luis2006; Acosta et al., Reference Acosta, Palma and Bahsas2010). Compounds of this type showed promising activity in vitro against Trypanosoma 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). As a continuation of our structural study of 2-substituted 1,4-epoxytetrahydro-1-benzazepines and as part of a program to identify structurally novel antiparasitic compounds with new modes of action to combat both T. cruzi and L. chagasi, here we report the synthesis and the X-ray powder diffraction (XRPD) data of the new compound 7-fluoro-2-exo-(2-methylpropen-1-yl)-2,3,4,5-tetrahydro-1,4-epoxybenzo[b]azepine.
The synthesis of this compound involved treating the corresponding 2-allyl-4-fluoro-N-(3-methylbut-2-enyl)aniline with an excess of hydrogen peroxide solution in the presence of catalytic amounts of sodium tungstate, and subsequent internal 1,3-dipolar cycloaddition of the resulting nitrone across the terminal C = C bond of the pendant allylic fragment, according to the methodology reported by Murahashi et al. (Reference Murahashi, Mitsui, Shiota, Tsuda and Watanabe1990).
II. EXPERIMENTAL
A. Synthesis
For the preparation of the title compound (Figure 1), sodium tungstate dihydrate (10 mol% Na2WO4.2H2O), followed by 30% aqueous hydrogen peroxide solution (30 mmol), were added to a stirred and cooled (ice-bath) solution of the 2-allyl-4-fluoro-N-(3-methylbut-2-enyl)aniline (10 mmol), 1a, in methanol (30 ml). The resulting mixture was stirred at 0 °C for 2 h and then at room temperature for an additional 6 h. The mixture was filtered and then extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and toluene (30 ml) was added to the organic black residue. The resulting solution was heated at reflux for 7 h. After cooling the solution to ambient temperature, the solvent was removed under reduced pressure and the crude product was purified by chromatography on silica gel using heptane-ethyl acetate (compositions in the range from 50:1 to 2:1 v/v) as eluent. The new compound 2a (M.p. 72 °C) was obtained as a colorless solid with a 35% yield.
Figure 1. Synthesis of the 7-fluoro-2-exo-(2-methylpropen-1-yl)-2,3,4,5-tetrahydro-1,4-epoxybenzo[b]azepine.
B. Powder data collection
A small amount of the new compound C14H16FNO 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 7-fluoro-2-exo-(2-methylpropen-1-yl)-2,3,4,5-tetrahydro-1,4-epoxybenzo[b]azepine 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 Loüer, Reference Boultif and Loüer2006) on a monoclinic cell with an absolute error of ±0.03°2θ in the calculations. The space group, P21/m (No. 11) was estimated by the CHEKCELL program (Laugier and Bochu, Reference Laugier and Bochu2002), which was compatible with the systematic absence and with the crystal density, 1.243 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 30 (Smith and Snyder, Reference Smith and Snyder1979) are compiled in Table II.
Figure 2. XRPD pattern of 7-fluoro-2-exo-(2-methylpropen-1-yl)-2,3,4,5-tetrahydro-1,4-epoxybenzo[b]azepine.
Table I. XRPD data of 7-fluoro-2-exo-(2-methylpropen-1-yl)-2,3,4,5-tetrahydro-1,4-epoxybenzo[b] azepine.
Table II. Crystal-structure data for 7-fluoro-2-exo-(2-methylpropen-1-yl)-2,3,4,5-tetrahydro-1,4-epoxybenzo[b] azepine.
ACKNOWLEDGEMENTS
This work was partially supported by Colciencias (Grant No. 1102-521-28229). The authors would like to acknowledge Miguel A. Ramos from Instituto Zuliano de Investigaciones Tecnológicas, INZIT (Maracaibo-Venezuela) for data collection. M.A. Macías and L.M. Acosta thank Colciencias for their doctoral fellowships.
