Crystal structure of 5,5-bis(4-methylbenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione monohydrate

Reaction of 4-methyl benzyl chloride with barbituric acid gave 5,5-bis(4-methylbenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione, which crystallized with two molecules in its asymmetric unit along with two solvent water molecules. A hydrogen-bonded sheet is formed by a combination of N—H⋯O and Owater—H⋯O hydrogen bonds, which are further interconnected by C—H⋯πaryl interactions, leading to a three-dimensional supramolecular architecture.


Chemical Context
Barbituric acid and its derivatives have historically been classified as compounds which act on the central nervous system (Barbachyn et al., 2007). These compounds have been widely used as therapeutic drugs such as anxiolytics, sedatives, hypnotics and anti-convulsants (Coupey, 1997). Recent investigations on barbituric acid derivatives revealed the applications of these compounds as antibacterial (Yilmaz et al., 2006;Sweidan et al., 2011), anti-viral (Clercq, 1986a,b;Baba et al., 1987), analgesic (Vida et al., 1975), anti-hypertensive (Bassin & Bleck, 2008) and as anti-cancer (Humar et al., 2004;Singh et al., 2009) agents. 5-Fluorouracil is a barbituric acid analogue, which has been widely employed as a clinically useful anti-cancer drug (Heidelberger & Arafield, 1963). Inspired by the above facts, the title compound was synthesized by Knoevenagel condensation reaction (Prajapati and Gohain, 2006). A double-benzylated product of barbituric acid was obtained by using two equivalents of 4-methyl benzyl chloride in the presence of catalytic amounts of 1,8-diazabicycloundec-7-ene (DBU) and solvent acetonitrile. The obtained compound was characterized by 1 H-NMR and mass spectroscopy. We report herein on its crystal structure.
There are several interesting differences between the two chemically closely related structures (I) and (II) (differing only by a methyl group on the two benzene rings). Firstly, (I) crystallizes in the orthorhombic space group Pca2 1 , whereas (II) crystallizes in the monoclinic space group P2 1 /n. Secondly, (I) crystallizes with two molecules in its asymmetric unit, while A view of (I), showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
A portion of the crystal packing viewed along [100] and showing two kinds of hydrogen-bonded (thin blue lines) sheets, each containing either A or B molecules. H atoms not involved in hydrogen bonding have been omitted for clarity. Table 1 Hydrogen-bond geometry (Å , ).
Thin-layer chromatography showed the absence of any starting material. The reaction mixture was cooled and poured into ice-cold water. The solid obtained was extracted with ethyl acetate and the organic layer was washed with saturated ammonium chloride solution and dried over anhydrous sodium sulphate. The solvent was removed under reduced pressure to give the title compound as a white solid (Yield 0.54 g, 91.83%). Colourless prisms of the title compound suitable for diffraction studies were grown from an ethyl acetate-petro-leum ether solvent system in the ratio 2.5:7.5, by the solvent evaporation technique.

Special details
Experimental. All the solvents employed were of analytical grade. Starting materials and reagents were purchased from Sigma Chemical co. (Saint Louis, USA). The reaction progress was monitored by thin layer chromatography using TLC Silica gel 60 F254 (Merck), and spots were visualized by using ultraviolet light of 254 nm. Melting point was determined by using open capillary and uncorrected value is given. 1H-NMR spectrum was recorded on Jeol-400 MHz NMR instrument using CDCl3/DMSO-d6 as solvent. Chemical shift values were expressed in δ (p.p.m.) relative to tetramethylsilane (TMS) as an internal reference standard. Mass spectrum of the compound was recorded on Shimadzu LC-2010EV with ESI probe. 1H-NMR spectral data of I clearly indicated the formation of I. In the spectrum, a singlet at δ (p.p.m.) value 2.23 corresponds to the two para-methyl groups, while, a singlet signal at δ (p.p.m.) value 3.22 is for four alkyl protons (two CH2 groups) and two doublets at 6.93 and 7.07 corresponds to the eight aromatic protons. Two NH protons of the barbituric acid moiety appeared at δ value 7.85 as a singlet. Mass spectrum of I gave a peak with (m/z) value = 335.0 which exactly matches with its calculated mass. Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.