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X-ray diffraction data of 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one and its synthetic precursor N-[4-(trifluoromethyl)phenyl]cinnamamide

Published online by Cambridge University Press:  10 June 2016

Jose H. Quintana Mendoza ,
J. A. Henao ,
Carlos E. Rondón Flórez ,
Carlos E. Puerto Galvis  and
Vladimir V. Kouznetsov
Jose H. Quintana Mendoza
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
Carlos E. Rondón Flórez
Affiliation:
Laboratorio de Química Orgánica y Biomolecular (LQOBio), Universidad Industrial de Santander, Parque Tecnológico Guatiguará, Km 2 vía refugio, Piedecuesta, A.A. 678, Bucaramanga, Colombia
Carlos E. Puerto Galvis
Affiliation:
Laboratorio de Química Orgánica y Biomolecular (LQOBio), Universidad Industrial de Santander, Parque Tecnológico Guatiguará, Km 2 vía refugio, Piedecuesta, A.A. 678, Bucaramanga, Colombia
Vladimir V. Kouznetsov
Affiliation:
Laboratorio de Química Orgánica y Biomolecular (LQOBio), Universidad Industrial de Santander, Parque Tecnológico Guatiguará, Km 2 vía refugio, Piedecuesta, A.A. 678, Bucaramanga, Colombia
*
a) Author to whom correspondence should be addressed. Electronic mail: jahenao@uis.edu.co

Abstract

The title compound, the 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (4) with chemical formula: (C16H12F3NO), was synthesized from N-[4-(trifluoromethyl)phenyl]cinnamamide (3), chemical formula: (C16H12F3NO), through an intramolecular cyclization mediated by triflic acid. Preliminary molecular characterization of both compounds was performed by Fourier transform infrared spectroscopy, gas chromatography mass spectrometry, and nuclear magnetic resonance spectroscopy (1H, 13C); crystallographic characterization was completed by X-ray diffraction of polycrystalline samples. The title compound 4 crystallized in a monoclinic system and unit-cell parameters are reported [a = 16.002 (3), b = 5.170 (1), c = 17.733 (3) Å, β = 111.11 (2)°, unit-cell volume V = 1368.5 (3) Å3, Z = 4] P21/c (No. 14) space group; the title compound 3 crystallized in a monoclinic system and unit-cell parameters are reported [a = 12.902 (2), b = 5.144 (1), c = 20.513 (5) Å, β = 91.67 (2)°, unit-cell volume V = 1360.7 (4) Å3, Z = 4] P21/c (No. 14) space group.

Keywords

cinnamamides2-quinolinonesintramolecular cyclizationX-ray powder diffraction data

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Type
New Diffraction Data
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Powder Diffraction , Volume 31 , Issue 3 , September 2016 , pp. 233 - 239
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Copyright
Copyright © International Centre for Diffraction Data 2016 

I. INTRODUCTION

Cyclic amides represent an important class of N-heterocycles prevalent in a myriad of natural products (Wang et al., Reference Wang, Peng, Qin, Zhao, Ma, Tung and Xu2015). In particular, 4-phenyl-2-quinolinones with important therapeutic properties (antiviral, antibiotic, anticancer, and antihypertensive) are the key structural moiety in a number of natural alkaloids, biologically active compounds, and pharmaceuticals (Joseph et al., Reference Joseph, Darro, Behard, Lesur, Collignon, Decaestecker, Frydman, Guillaumet and Kiss2002) (Figure 1).

Figure 1.

(Color online) Natural and synthetic amides with significant biological activities.

In addition, acyclic amides are also widely prevalent in both naturally occurring and synthetic compounds, being present in 25% of the available drugs (Roughley and Jordan et al., Reference Roughley and Jordan2011). It is the case of avenanthramides, a group of secondary metabolites isolated from oats (Avena Sativa), with promising antioxidant activity (Lee-Manion et al., Reference Lee-Manion, Price, Strain, Dimberg, Sunnerheim and Welch2009) (Figure 1).

Although some methods are available for the synthesis of cyclic and acyclic amides (Kadnikov and Larock, Reference Kadnikov and Larock2004; Lanigan et al., Reference Lanigan, Starkov and Sheppard2013), the straightforward routes for constructing 4-phenyl-2-quinolinones from cinnamamides, such as avenanthramide analogues, are highly attractive. Herein, we want to report the X-ray powder diffraction (XRPD) for the compound N-[4-(trifluoromethyl)phenyl]cinnamamide (3), prepared using commercial reagents, and for 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (4) synthesized from (3) through an intramolecular cyclization mediated by triflic acid, exploring the less-known crystallographic information by X-ray diffraction about this type of derivative.

II. EXPERIMENTAL

A. Synthesis

The N[(4-(trifluoromethyl)phenyl]cinnamamide (3): An amount of 1.6 g of 4-(trifluoromethyl)aniline (1) (10.2 mmol) was dissolved in CH2Cl2 (45 ml) and a solution of cinnamoyl chloride (2) (1.1 g, 7.2 mmol) in CH2Cl2 (5 ml) was added dropwise at 0 °C for 2 h. After the mixture was stirred for the indicated time, the solvent was removed under reduced pressure and the residue was redissolved in AcOEt (15 ml) and washed with aqueous solutions of NaHCO3 (15 ml, 1 M) and HCl (15 ml, 1 M), dried over MgSO4, filtered, and concentrated under reduced pressure to afford the N-[4-(trifluoromethyl)phenyl]cinnamamide (1.99 g, 95%). White crystals were obtained from hexane–ethyl ethanoate (AcOEt) 5:1 (Figure 2).

Figure 2.

Coupling reaction between 4-(trifluoromethyl)aniline and cinnamoyl chloride.

White crystals (1.99 g, 6.83 mmol, 95%), R f [hexane–EtOAc 3:1] = 0.4; IR (ATR, cm−1): 3325 ν (NH), 1661 ν (C=O), 1621 ν (C=C), 1323 ν (C–N), 1250 ν (C–F) 831 ν(C=C–H); 1H NMR (400 MHz, CDCl3), δ (ppm): 7.79 (1H, d, J = 15.6 Hz, =CHPh), 7.76 (2H, d, J = 9.4 Hz, 4′ and 6′-H Ar), 7.60 (2H, d, J = 8.6 Hz, 3′ and 7′-H Ar), 7.59 (1H, s, NH), 7.54 (2H, dd, J = 7.0, 2.6 Hz, 5 and 9-H Ar), 7.41–7.38 (3H, m, 6, 7, and 8-H Ar), 6.57 (1H, d, J = 15.5 Hz, =CHCO); 13C NMR (101 MHz, CDCl3), δ (ppm): 164.2, 143.6 (+), 141.2, 141.1, 134.4, 130.4 (2C, +), 129.1 (2C, +), 128.2 (2C, +), 126.5 (2C, q, J = 3.8 Hz, +), 124.2 (d, J = 271.7 Hz), 120.2 (+), 119.6 (+). Gas chromatography (GC): R t = 26.385 min, mass spectrometry (MS) (EI), m/z (%): 291 (M+·, 23), 132 (15), 131 (100), 103 (60), 77 (35).

The 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (4): Triflic acid (20-fold excess) was added to a stirred solution of the N-[4-(trifluoromethyl)phenyl]cinnamamide in CHCl3 (2 mmol/10 ml), and the reaction mixture was heated under gentle reflux until no starting material was present by TLC (6 h). The reaction mixture was cooled to room temperature, and water (10 ml) was added. The mixture was basicified with an excess of solid NaHCO3 until pH 7. The product was extracted into EtOAc (3 × 10 ml), dried over MgSO4, concentrated under reduced pressure, and purified by column chromatography on silica gel with petroleum ether/ethylacetate (3:1) to afford the 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (0.33 g, 58%). White crystals were obtained from hexane–EtOAc 3:1 (Figure 3).

Figure 3.

Cyclization of N-[4-(trifluoromethyl)phenyl]cinnamamide promoted by triflic acid (TfOH).

White crystals (0.33 g, 1.13 mmol, 58%), R f [hexane–EtOAc 3:1] = 0.06; IR (ATR, cm−1): 3184 ν (NH), 2973 ν (CH), 1685 ν (C=O),, 1325 ν (C–N), 1262 ν (C–F); 1H NMR (400 MHz, CDCl3) δ (ppm): 9.90 (1H, s, 5-H Ar), 7.47 (1H, d, J = 8.3 Hz, 7-H Ar), 7.41–7.27 (3H, m, 11, 12, and 13-H Ar), 7.20 (2H, s, 10 and 14-H Ar), 7.18 (1H, s, NH), 7.02 (1H, d, J = 8.3 Hz, 8-H Ar), 4.35 (1H, t, J = 7.4 Hz, 4-H), 2.98 (dd, J = 7.4, 4.6 Hz, 3a and 3b-H); 13C NMR (101 MHz, CDCl3), δ (ppm): 171.5, 140.5 (2C), 140.1, 129.3 (2C, +), 127.7 (2C, +), 127.4 (d, J = 70.9 Hz, +), 125.6, 125.6 (q, J = 3.8 Hz, +), 125.5–125.4 (m, J = 6.6, 2.7 Hz), 122.7, 116.1 (+), 41.9 (+), 38.24 (+).GC: R t = 24.265 min, MS (EI), m/z (%): 291 (M+, 100), 290 (23), 263 (36), 262 (73), 248 (53).

B. Powder data collection

The title compounds 3 and 4 were ground and sieved to a grain size <38 µm. The compounds were mounted on a zero-background specimen holder. The diffraction patterns were collected at room temperature (298 K) in the 2θ range from 2 to 70°2θ with a step size of 0.015 26°2θ and a count time of 1.0 s step−1, using a Bruker D8 Advance DaVinci X-ray diffractometer operating in Bragg–Brentano geometry equipped with an X-ray tube (CuKα1 radiation: λ = 1.5406 Å, 40 kV, and 30 mA) with a nickel filter and a one-dimensional LynxEye detector. A fixed divergence slit of 0.6 mm and primary and secondary soller slits of 2.5° were used. 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 peak observed positions and intensities.

III. RESULTS AND DISCUSSION

The experimental XRPD patterns of the title compounds 3 and 4 are depicted in Figures 4 and 5 respectively and their XRPD data are given in Table I (compound 3) and Table II (compound 4). Indexing of the experimental XRPD patterns were done using the DICVOL06 program (Boultif and Louër, Reference Boultif and Loüer2004) with an absolute error of 0.03°2θ. The title compounds 3 and 4 crystallized in a monoclinic system with space group P21/c (No.14) estimated by the CHEKCELL program (Laugier and Bochu, Reference Laugier and Bochu2002), which were compatible with the systematic absences and with the crystal density [1.422 g cm−3 (3) and 1.413 g cm−3 (4)]. The unit-cell parameters were refined with the NBS*AIDS83 program (Mighell et al., Reference Mighell, Hubbard and Stalick1981). Unit-cell data, values of M 20 (de Wolff, Reference de Wolff1968), and F 30 (Smith and Snyder, Reference Smith and Snyder1979) are presented in Table III.

Figure 4.

XRPD pattern of N-[4-(trifluoromethyl)phenyl]cinnamamide (3).

Figure 5.

XRPD pattern of 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (4).

Table I.

XRPD data of N-[4-(trifluoromethyl)phenyl]cinnamamide (3).

Table II.

XRPD data of 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (4).

Table III.

Crystal-structure data for N-[4-(trifluoromethyl) phenyl] cinnamamide (3) y 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (4).

SUPPLEMENTARY MATERIAL

The supplementary material for this article can be found at http://dx.doi.org/10.1017/S0885715616000282.

ACKNOWLEDGEMENTS

This work was financially supported by Colciencias under the project No. RC-0346-2013. Authors express their acknowledgement to Universidad Industrial de Santander-UIS and Laboratorio de Rayos-X del Parque Tecnológico Guatiguará adscrito a la Vicerrectoría de Investigación y Extensión de la Universidad Industrial de Santander-UIS. CEPG thanks the scholarship given by the doctoral program Colciencias-Conv. 617.

References

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Figure 0

Figure 1. (Color online) Natural and synthetic amides with significant biological activities.

Figure 1

Figure 2. Coupling reaction between 4-(trifluoromethyl)aniline and cinnamoyl chloride.

Figure 2

Figure 3. Cyclization of N-[4-(trifluoromethyl)phenyl]cinnamamide promoted by triflic acid (TfOH).

Figure 3

Figure 4. XRPD pattern of N-[4-(trifluoromethyl)phenyl]cinnamamide (3).

Figure 4

Figure 5. XRPD pattern of 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (4).

Figure 5

Table I. XRPD data of N-[4-(trifluoromethyl)phenyl]cinnamamide (3).

Figure 6

Table II. XRPD data of 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (4).

Figure 7

Table III. Crystal-structure data for N-[4-(trifluoromethyl) phenyl] cinnamamide (3) y 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (4).

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