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Synthesis and X-ray diffraction data of 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile, (C15H20N2O4)

Published online by Cambridge University Press:  23 May 2016

Jose H. Quintana Mendoza ,
J. A. Henao ,
Aurora L. Carreño Otero  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
Aurora L. Carreño Otero
Affiliation:
Laboratorio de Química Orgánica y Biomolecular (LQOBio), Universidad Industrial de Santander, Parque Tecnológico Guatiguara, Km 2 via refugio, Piedecuesta, Colombia
Vladimir V. Kouznetsov
Affiliation:
Laboratorio de Química Orgánica y Biomolecular (LQOBio), Universidad Industrial de Santander, Parque Tecnológico Guatiguara, Km 2 via refugio, Piedecuesta, Colombia
*
a) Author to whom correspondence should be addressed. Electronic mail: jahenao@uis.edu.co

Abstract

The α-aminonitrile, 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile (C15H20N2O4), was prepared through a silica sulfuric acid-catalyzed Strecker reaction between 3,4,5-trimethoxybenzaldehyde, morpholine, and two different cyanide sources. Molecular characterization was performed by Fourier transform infrared spectroscopy, gas chromatography–mass spectrometry, (1H, 13C – mono and bidimensional) nuclear magnetic resonance; crystallographic characterization was completed by X-ray powder diffraction of polycrystalline samples. The title compounds crystallized in a monoclinic system and unit-cell parameters are reported [a = 13.904(2), b = 5.1696(6), c = 21.628(3) Å, β = 104.31(1)°, unit-cell volume V = 1506.3(3) Å3, Z = 4]. All measured lines were indexed with the P21/a (No. 14) space group.

Keywords

α-Aminonitrilesgirgensohnine alkaloidX-ray powder diffraction data

Information

Type
New Diffraction Data
Information
Powder Diffraction , Volume 31 , Issue 2 , June 2016 , pp. 149 - 152
Copyright
Copyright © International Centre for Diffraction Data 2016 

I. INTRODUCTION

Strecker reaction, studied using different Lewis acids (Royer et al., Reference Royer, De and Gibbs2005; Surya et al., Reference Surya Prakash, Mathew, Panja, Alconcel, Vaghoo, Do and Olah2007) or bases (Takahashi et al., Reference Takahashi, Fujisawa, Yanai and Mukaiyama2005) as catalysts, and NaCN, KCN, trimethylsilylcyanide, acetone cyanohydrin as cyanide sources, provides an important tool for construction of small and functionalized nitrogen-containing molecules as the α-aminonitriles. The α-aminonitriles are key intermediates for synthesis of natural and un-natural aminoacids and compounds of great interest that show remarkable biological activities (Chaturvedi et al., Reference Chaturvedi, Chaturvedi, Mishra and Mishra2012) such as anticancer, antifungal, antibiotic, etc. The alkaloid girgensohnine, racemic piperidinic α-aminonitrile, is a cyanogenic metabolite extracted with a yield of no more than 0.05% from Girgensohnia oppositiflora (Amaranthaceae), shrub that grows in the Russia and Iran deserts. There are not many studies related to the synthesis of compounds structurally related to this alkaloid (Vargas Méndez and Kouznetsov, Reference Vargas Méndez and Kouznetsov2013).

In searching for safer and environmentally friendly protocol to preparing the 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile, the Strecker reaction was performed using acetone cyanohydrin as a cyanide source and silica sulfuric acid (SSA) as catalyst, in MeCN at room temperature for over 20 h (Figure 1). Structural elucidation was made using spectroscopic techniques [Fourier transform infrared spectroscopy (FTIR), gas chromatography–mass spectrometry (GC–MS), proton nuclear magnetic resonance (1H NMR), and carbon-13 nuclear magnetic resonance (13C NMR)] allowing the identification of the main spectral features (the CN function, hydrogen linked with nitrile group, aromatic, and N-heterocyclic protons) of these compounds. The X-ray powder diffraction (XRPD) data are reported. Crystallographic information by X-ray diffraction about this type of derivative has been little explored.

Figure 1.

Preparation of 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile (1).

II. EXPERIMENTAL

A. Synthesis

The analog of girgensohnine alkaloid was prepared via one-pot reaction mode. An equimolar mixture of 3,4,5-trimethoxybenzaldehyde (1 mmol) and morpholine (1.1 mmol) was stirred. The acetone cyanohydrin (1.5 mmol) and the catalyst SSA (1:1 by weight) were then added in acetonitrile (15 ml) at room temperature (20 h, 30 min). The progress of the reaction was monitored by thin layer chromatography (TLC) (ether:ethyl acetate, 10:1). Then, the reaction mixture was filtered and evaporated of the solvent, the residue was purified by column chromatography on alumina (100–200 mesh) eluting with petroleum ether:ethyl acetate (15:1) to furnish title compound as white solid.

2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile ( 1 ). Yield: 77%, mp: 137–139 °C. IR (KBr): 2224 v (C≡N), 1248 v (N-C) cm−1. 1H NMR (DMSO-d6, 400 MHz) δ (ppm): 6.74 (2H, s, 2,6-HAr), 4.74 (1H, s, 10-H), 3.87 (6H, s, 3,5-OCH3), 3.83 (3H, s, 4-OCH3), 3.79–3.66 (4H, m, 3,5-HMorph), 2.68–2.43 (4H, m, 2,6-HMorph). 13C NMR (100 MHz) δ (ppm): 153.7 (3,5-CAr), 138.5 (4-CAr), 128.2 (1-CAr), 115.5 (-CN), 105.1 (+, 2,6-CAr), 66.9 (−, 3,5-CMorph), 62.8 (+, 10-C), 61.2 (+, 4-OCH3), 56.5 (+, 3–5-OCH3), 50.3 (−, 2,6-CMorph). GC–MS (70 eV): tR = 21.3 min, m/z = (292, M+), 207 (52), 206 (100), 176 (14), 86 (20), 66 (14). Anal.Calcd. (analytically calculated) for C15H20N2O4: C, 61.63; H, 6.90; N, 9.58; Found: C, 61.47; H, 6.63; N, 9.45.

B. Powder data collection

The title compound was ground and sieved to a grain size less than 38 µm. Powder diffraction pattern was recorded at room temperature (298 K) on a BRUKER D8 ADVANCE diffractometer working in the Bragg-Brentano geometry using CuKα radiation (λ = 1.541 84 Å), operating at 40 kV and 40 mA. The pattern was recorded in steps of 0.0156° (2θ), from 5° to 50° at 0.8 s step−1. The diffractometer was equipped with the primary and secondary Soller slits of 2.5°, divergence slit of 0.6 mm, Ni filter of 0.02 mm, and a LynxEye detector.

III. RESULTS AND DISCUSSION

The experimental XRPD pattern of the title compound (Figure 1, compound 1) is depicted in Figure 2 and the XRPD data are given in Table I. Powder X program (Dong, Reference Dong1999) was used to remove the background (Sonneveld and Visser, Reference Sonneveld and Visser1975), smooth the profile (Saviztky and Golay, Reference Saviztky 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. The indexing of the pattern was performed with the program DICVOL06 (Boultif and Loüer, Reference Boultif and Loüer2004) with an absolute error of 0.03°(2θ). The title compound crystallized in a monoclinic system with space group P21/a (No. 14) estimated by the CHEKCELL program (Laugier and Bochu, Reference Laugier and Bochu2002), which was compatible with the systematic absences. The calculated density for Z = 4 is in accordance with the measured value, D m = 1.29 g cm−3. The analysis of the entire pattern (111 diffraction maxima) with NBS*AIDS83 (Mighell et al., Reference Mighell, Hubberd and Stalick1981) resulted in a unit cell with parameters: a = 13.904(2), b = 5.1696(6), c = 21.628(3) Å, β = 104.31(1)°, and V = 1506.3(3) Å3. The set of reflections observed are consistent with space group P21/a (No. 14). The de Wolf (de Wolff, Reference De Wolff1968) and Smith–Snyder (Smith and Snyder, Reference Smith and Snyder1979) figures of merit were M 20 = 54.1 and F 30 = 151.4(0.0051, 39), respectively. The parameters of the unit cell are compiled in Table II.

Figure 2.

X-ray powder diffraction pattern of 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile (1).

Table I.

X-ray powder diffraction data of 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile (1).

Table II.

Parameters obtained by X-ray powder diffraction for 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile (1).

SUPPLEMENTARY MATERIAL

To view supplementary material for this article, please visit http://dx.doi.org/10.1017/S0885715616000075

ACKNOWLEDGEMENTS

This work was supported by internal grant 9309 (VIE-UIS). Authors express their acknowledgement to Universidad Industrial de Santander (UIS), Vicerrectoría de Investigación y Extensión (VIE) and Parque Tecnológico Guatiguará (PTG), Bucaramanga, Colombia for data collection. José H. Quintana Mendoza thanks COLCIENCIAS and Universidad Industrial de Santander for his scholarship (Programa Jóvenes Investigadores e Innovadores, año 2013).

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Figure 0

Figure 1. Preparation of 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile (1).

Figure 1

Figure 2. X-ray powder diffraction pattern of 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile (1).

Figure 2

Table I. X-ray powder diffraction data of 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile (1).

Figure 3

Table II. Parameters obtained by X-ray powder diffraction for 2-morpholino-2-(3,4,5-trimethoxyphenyl)acetonitrile (1).

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