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X-ray powder diffraction data for 1-methylhydantoin, an antiasthmatic and antidepressive hydantoin compound

Published online by Cambridge University Press:  23 April 2015

Gerzon E. Delgado ,
Asiloé J. Mora ,
Jines E. Contreras  and
Cecilia Chacón
Gerzon E. Delgado*
Affiliation:
Laboratorio de Cristalografía, Departamento de Química, Facultad de Ciencias, Universidad de Los Andes, Mérida, 5101, Venezuela
Asiloé J. Mora
Affiliation:
Laboratorio de Cristalografía, Departamento de Química, Facultad de Ciencias, Universidad de Los Andes, Mérida, 5101, Venezuela
Jines E. Contreras
Affiliation:
Laboratorio de Cristalografía, Departamento de Química, Facultad de Ciencias, Universidad de Los Andes, Mérida, 5101, Venezuela
Cecilia Chacón
Affiliation:
Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada-Instituto Politécnico Nacional, México D.F. 11500, México
*
a)Author to whom correspondence should be addressed. Electronic mail: gerzon@ula.ve
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Abstract

X-ray powder diffraction data, unit cell parameters, and space group for 1-methylhydantoin, C4H6N2O2, are reported [a = 5.6070(9) Å, b = 12.170(1) Å, c = 8.097(1) Å, β = 105.41(1), Z = 4, unit cell volume V = 532.66(9) Å3, with M20 = 50.2 and F30 = 62.2 (0.0082, 59)]. All measured lines were indexed and are consistent with the monoclinic P21/c space group.

Keywords

X-ray powder diffraction1-methylhydantoinantiasthmaticantidepressive
Type
New Diffraction Data
Information
Powder Diffraction , Volume 30 , Issue 2 , June 2015 , pp. 178 - 181
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Copyright
Copyright © International Centre for Diffraction Data 2015 

I. INTRODUCTION

The imidazolidine-2,4-dione, or hydantoin, is a common 5-member ring containing a reactive cyclic urea core (López and Trigo, Reference López and Trigo1985; Meusel and Gütschow, Reference Meusel and Gütschow2004). This heterocycle represents a significant molecular template in combinatorial chemistry libraries (Park et al., Reference Park, Ehrler, Spoerri and Kurth2001), due principally to the four possible points of substitutions. The biological activities of hydantoin derivatives have been recognized for a long time, and are responsible for a wide variety of biological behavior due principally to its wide range of therapeutic properties (Mutschler and Derendorf, Reference Mutschler and Derendorf1995). The best known hydantoin, 5,5-diphenylhydantoin or phenytoin, has been the most widely used antiepileptic drug since the experimental determination of its anticonvulsant properties (Merrit and Putnam, Reference Merrit and Putnam1938).

Particularly, 1-methylhydantoin (Figure 1) is a hydantoin produced by bacterial creatinine deaminase in the intestinal tract of uremic patients (Yang et al., Reference Yang, Liu, Li, Liu, Peng and Jiang2007), and was found as a metabolite of the intelligence affecting substance dupracetam, a nootropic drug from the racetam family (Baune and Renger, Reference Baune and Renger2014). Recently, for this molecule has been found to have excellent antiasthmatic and antitussive effects (Han et al., Reference Han, Dong and Qiu2014) and antidepressant properties (You et al., Reference You, Zhang, Wang, Shi, Guo, Shi, Hou and Liu2013).

Figure 1. Structural formula of 1-methylhydantoin. Ring atoms are numbered 1-5.

For this compound, experimental and theoretical vibrational study using DFT calculation was performed (Nogueira et al., Reference Nogueira, Ildiz, Canotilho, Eusébio and Fausto2014), and the crystal structure of 1-methylhydantoin was reported (Puszynska-Tuszkanow et al., Reference Puszynska-Tuszkanow, Daszkiewicz, Maciejewska, Staszak, Wietrzyk, Filip and Cieslak-Golonka2011), CSD-database refcode EWUVEY (Allen, Reference Allen2002; CSD, 2014), crystallizing in the monoclinic space group P21/c (No. 15). However, the only experimental pattern in the ICDD Powder Diffraction File (00-013-0685) (ICDD, Reference Kabekkodu2011) no precise unit cell data, and only d-spacings were reported.

In continuation of our previous investigation on hydantoin derivative compounds (Delgado et al., Reference Delgado, Mora, Uzcátegui, Bahsas and Briceño2007, Reference Delgado, Seijas and Mora2012, Seijas et al., Reference Seijas, Mora, Delgado, Brunelli and Fitch2010), the present work is focused on report the spectroscopic characterization [Fourier-transform infrared (FTIR), nuclear magnetic resonance (NMR)], thermal analysis (TGA-DSC), and X-ray powder diffraction data for 1-methylhydantoin.

II. EXPERIMENTAL

1-methylhydantoin 99% was a commercial material, purchased from Aldrich Co. (M49887), and was used as-received (m.p. 156–157 °C).

A. FTIR and NMR spectroscopy

The FTIR absorption spectrum was obtained as KBr pellet using a Perkin-Elmer 1600 spectrometer. 1H-NMR and 13C-NMR spectra were recorded on a Bruker Avance 400 model spectrometer in DMSO-d6 solution. Infrared spectrometry showed stretching vibrations; 3439.0 cm−1 [t, N-H], 3428.5 cm−1 [t, N-H], 1768.6 cm−1 [t, C = O], 1707.9 cm−1 [t, C = O], 1500.1 cm−1 [t, N-H], 1454.4 [t, C-N], and NMR; 1H NMR (400 MHz, DMSO-d6) δ = 10.69 (s, CH3), δ = 3.91 (s, CH2), δ = 2.79 (s, NH). 13C NMR (100.6 MHz, DMSO-d6) δ = 171.67 (C2), 157.00 (C4), δ = 52.41 (C5), 28.65 (C6).

B. Thermal analysis

Thermal analysis of 1-methylhydantoin was performed in a thermal analyzer SDT Q600. Sample, 7.56 mg, was heated from 25 to 600 °C at a rate of 10 °C min−1, under a nitrogen flux of 100 ml min−1. A sharp endothermic peak observed at 156.6 °C corresponds to melting of the compound. The hydantoin compound decomposed completely at 242.7 °C.

C. X-ray powder diffraction data

For the X-ray analysis, a small quantity of the sample was ground mechanically in an agate mortar and pestle. The resulting fine powder, sieved to 106 μm, was mounted on a flat zero-background holder covered with a thin layer of petroleum jelly. The X-ray powder diffraction data was collected at room temperature 293(1) K, in θ/θ reflection mode using a Philips diffractometer with PW-1150/25 goniometer and monocromatized CuKα radiation (λ = 1.5418 Å). The diffractometer was operated at 40 kV and 25 mA. The specimen was scanned from 5° to 60°2θ, with a step size of 0.02° and counting time of 10 s per step. Silicon (SRM 640) was used as an external standard. The software package HIGHSCORE PLUS V2.0 (PANalytical, Almelo, Netherlands) was used to eliminate the Kα 2 component, establish the positions of the peaks and to determine the peak intensities of the diffraction peaks.

III. RESULTS AND DISCUSSION

The X-ray powder pattern of 1-methylhydantoin is shown in Figure 2. The 20 first peak positions were indexed using the program DICVOL06 (Boultif and Louër, Reference Boultif and Louër2004), which gave a unique solution in a monoclinic cell. This result confirms the crystal structure reported (Puszynska-Tuszkanow et al., Reference Puszynska-Tuszkanow, Daszkiewicz, Maciejewska, Staszak, Wietrzyk, Filip and Cieslak-Golonka2011). The complete powder diffraction dataset was reviewed in the monoclinic space group P21/c (No. 15), using the program NBS*AIDS83 (Mighell et al., Reference Mighell, Hubbard and Stalick1981). All measured lines were indexed and were consistent with the mentioned space group. From this analysis, the refined unit cell parameters obtained were: a = 5.6070(9) Å, b = 12.170(1) Å, c = 8.097(1) Å, β = 105.41(1), V = 532.66(9) Å3, Z = 4, with figures of merit M20 = 50.2 (de Wolff, Reference de Wolff1968) and F 30 = 62.2 (0.0082, 59) (Smith and Snyder, Reference Smith and Snyder1979). The resulting X-ray powder diffraction data for 1-methylhydantoin, together with the observed and calculated 2θ, the d-spacing's as well as the relative intensities of the reflections, are given in Table I. In order to confirm the unit cell parameters, a Le Bail refinement (Le Bail, Reference Le Bail2005) was carried out using the FULLPROF program (Rodríguez-Carvajal, Reference Rodriguez-Carvajal2014). Figure 3 shows the very good fit between the observed and calculated patterns.

Figure 2. X-ray powder diffraction pattern of 1-methylhydantoin.

Figure 3. (Color online) Le Bail refinement of 1-methylhydantoin.

Table I. X-ray powder diffraction data of 1-methylhydantoin.

ACKNOWLEDGEMENTS

This work was supported by Consejo de Desarrollo Científico, Humanístico y Tecnológico (CDCHTA-ULA, grant C-1922-15-08-A), and FONACIT (Fondo Nacional de Investigaciones Científicas, grant LAB-97000821) in Venezuela.

SUPPLEMENTARY MATERIALS AND METHODS

The supplementary material for this article can be found at http://www.journals.cambridge.org/PDJ.

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Figure 0

Figure 1. Structural formula of 1-methylhydantoin. Ring atoms arenumbered 1-5.

Figure 1

Figure 2. X-ray powder diffraction pattern of 1-methylhydantoin.

Figure 2

Figure 3. (Color online) Le Bail refinement of 1-methylhydantoin.

Figure 3

Table I. X-ray powder diffraction data of 1-methylhydantoin.

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