The Crystal and Molecular Structure of 1-Methyl-4- -(p-methylbenzylidene)-2-methylseleno-5-imidazolinone

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1 Polish J. Chem., 74, (2000) ORGANIC CHEMISTRY The Crystal and Molecular Structure of 1-Methyl-4- -(p-methylbenzylidene)-2-methylseleno-5-imidazolinone by E. es³awska 1, B.J. Oleksyn 2, M.J. Korohoda 1 and J. Œliwiñski 2 1 Department of Chemistry, Pedagogical University, Podchor¹ ych 2, Kraków, Poland 2 Faculty of Chemistry, Jagiellonian University, R. Ingardena 3, Kraków, Poland (Received December 22nd, 1999) The crystal structure of 1-methyl-4-(p-methylbenzylidene)-2-methylseleno-5-imidazolinone has been determined by X-ray diffraction methods. The crystals are triclinic, space group P 1, with a = 8.130(1) Å, b = 8.888(1) Å, c = 9.287(1) Å, = 93.80(1), = 94.86(1), = 92.67(1), Z = 2. The molecule is approximately planar with most of the bonds participating in a conjugated system, stabilized by weak intramolecular hydrogen bond, C8 H8 N1. Conclusions about electron distribution within this system have been drawn from the bond angles and bond lengths. In the unit cell, molecular pairs can be discerned with antiparallel imidazole rings in the distance of 3.5. Key words: derivatives of hydantoin, selenoorganic compounds, crystal and molecular structures The title compound is a derivative of hydantoin (1), which is a core molecular fragment of phenytoin and related compounds with important biological activities (Fig. 1). Phenytoin (5,5-diphenylhydantoin) is one of the most widely used anticonvulsants. According to [1], the site of action of phenytoin is the neuronal voltage-sensitive sodium channel. However, no exact information about the location and nature of this site has been collected so far. The relationship between the molecular structure and activity has been thoroughly studied for phenytoin and its derivatives [1 3]. A general model compound with anticonvulsant activity, proposed in [2], comprises two aromatic rings or their equivalents in a suitable orientation and a third, heterocyclic region, usually a cyclic imid. Evaluation of binding to the neuronal voltage-dependent sodium channel together with conformational studies for hydantoin and diphenylhydantoin derivatives revealed their optimum molecular conformation. According to these studies, one of the phenyl rings should be almost coplanar with the hydantoin moiety [1]. Activity of derivatives of hydantoin at serotonin receptors (5 HT 1D and 5 HT 2A ) was studied by Glen et al. [4], who postulated a pharmacophore composed of a protonated amine site, an aromatic site, a hydrophobic pocket and two hydrogen-bonding sites. As suggested by Kolasa et al. [5], also benzylidene derivatives of hydantoin, which have a methylene bridge (to the phenyl ring) at the 5-position, are weak anticonvulsants. Only few crystal structures of these derivatives have been studied, some of them annelated in the amide fragment by adding a five-membered heterocyclic ring with sulfur [6 13].

2 752 E. es³awska et al. This work is a continuation of the studies on the benzylidene derivatives of hydantoin, in which oxygen at position 2 is replaced by S, Se (2)orSe CH 3 (3) (Fig. 1). The crystal structure of derivative 2 withx=sewasdescribed earlier [14] together with modelling studies of the molecules withx=oors.inorder to characterize the influence of X and the substituent in the benzene ring on the molecular and crystal structure of the studied derivatives, we have undertaken the X-ray crystal structure analysis of the compound (3) (Fig. 1). Figure 1. Structural formulae of hydantoin (1), 5-p-chlorobenzylidene-3-methyl-2-X-hydantoin (2), and 1-methyl-4-(p-methylbenzylidene)-2-methylseleno-5-imidazolinone (3). EXPERIMENTAL The title compound was obtained by the method described previously [15]. The bright yellow, glittering, single crystals of tabular shape were grown from ethanol/dmso by slow evaporation. They were combinations of forms: {111}, {-111}, {011}, {0-11}, {102}, {-102}, and {100}. One of them, with dimensions mm, was mounted on a KM-4 automatic single crystal diffractometer (KUMA Diffraction, Poland), equipped with graphite monochromator, which was used for the intensity data collection with CuK radiation. The lattice parameters and their standard deviations were determined by the least-squares analysis from the setting angles of 67 reflections, which were confined in the 2 range of to Relevant crystallographic data, together with information about data collection and structure refinement, are listed in Table 1. Data reduction with corrections for Lorentz and polarization effects, but not for absorption, was perfomed using local KM-4 software. The linear absorption coefficient, µ, has a moderate value, but the anisotropy of the crystal size causes that the transmission factor changed in the range of According to Jones [16], this may lead to the apparent highly anisotropic thermal motion of atoms, but the atomic positions are not severely affected. At the same time, the accuracy of the final parameters may be overestimated, because of systematic errors introduced by uncorrected effects of absorption. Regrettably, the absorption correction could not be applied for the investigated crystal, because of lack of the appropriate programs at our disposal. However, the displacement parameters for all the non-hydrogen atoms in the asymmetric unit are neither too large nor very anisotropic (e.g. for Se they are: U 11 = (2), U 22 = (2), U 33 = (2), U 23 = (2), U 13 = (2), U 12 = (2)), which suggests that the neglect of absorption effects had probably not a very serious influence on other parameters. The structure was solved by direct methods using SHELXS86 [17] system of programs. The full-matrix least-squares refinement of the structure was conducted on F 2 values with the use of SHELXL93 [18] for all the unique reflections. The difference Fourier map after the anisotropic refinement of the non-hydrogen atoms revealed the positions of all hydrogen atoms, which were then refined isotropically. The weighting scheme was w 1 = 2 (F o ) 2 + (0.0622P) P, where P = (F 2 F )/3. o c

3 The crystal and molecular structure of ' The extinction correction,, which is given in SHELXL93 by the formula F c = kf c [ F 2 c 3 /sin2 ] 1/4 refined to the value (7). The drawings were made with the use of ZORTEP programme [19]. Table 1. Crystallographic parameters and experimental data for 1-methyl-4-(p-methylbenzylidene)-2-methylseleno-5-imidazolinone. Molecular formula C 13 H 14 N 2 OSe Formula weight Temperature 293 K Crystal system triclinic Space group P 1 Unit cell dimensions a = 8.130(1) Å = 93.80(1) b = 8.888(1) Å = 94.86(1) c = 9.287(1) Å = 92.67(1) Volume (14) Å 3 Z 2 Density (calculated) g/cm 3 Wavelength Å Absorption coefficient cm 1 F(000) for data collection 2.00 to hkl range 10 h k l 11 Reference reflections number 3 (1 1 1, 2 2 1, 30 1) frequency every 50 reflections stability 3% Number of reflections collected 5752 unique 2729 (R int = ) Data/Number of parameters 2729/211 Final R(F) wr(f 2 ) S max. shift/e.s.d max/min/eå / 0.62 RESULTS AND DISCUSSION The projection of molecule 3 on the plane of the five-membered ring is given in Fig. 2, while the unit cell packing is depicted in Fig. 3. The final coordinates for non-hydrogen atoms are listed in Table 2. Table 3 contains the values of bond lengths and bond angles.

4 754 E. es³awska et al. Figure 2. Atom numbering scheme of the molecule of 1-methyl-4-(p-methylbenzylidene)-2-methylseleno-5-imidazolinone. Probability level for the thermal ellipsoids is 50%. Figure 3. Packing of molecules in the unit cell of the crystalline 1-methyl-4-(p-methylbenzylidene)-2- methylseleno-5-imidazolinone projected along the X axis. Hydrogen bonds are denoted by broken lines. The bond lengths have typical values. Comparison of the N C and C C distances in the five-membered ring with those reported in [20] suggests that electron delocalization in 3 is slightly less pronounced than in other imidazole-like systems. Nevertheless, the system of bonds O1=C4 N3 C2=N1 C5 seems to be conjugated with the benzylidene fragment, as suggested by the bond lengths (Table 3). The bonds formed by the selenium atom with C2 and C14 are comparable with those reported in [20] for C(sp 3 ) Se and C(sp 2 ) Se, which have average values: 1.97(3) Å and 1.89(1) Å, respectively. Both Se C2 and Se C14 are definitely single bonds in contrast to the double bond, Se=C2, of length 1.811(3) Å, observed in compound 2 withx=se[14].

5 The crystal and molecular structure of Table 2. Atomic coordinates ( 10 4 ) for non-hydrogen atoms and equivalent isotropic displacement parameters (Å ). U eq is defined as one third of the orthogonalized U ij tensor. Atom x y z Ueq N1 5681(2) 228(2) 7335(2) 418(4) C2 5040(3) 1024(2) 7020(2) 412(4) Se (4) (3) (3) 648(2) C (4) 27(4) 8714(4) 715(8) N3 5879(2) 1859(2) 6085(2) 424(4) C (4) 3277(3) 5491(3) 522(5) C4 7233(3) 1078(2) 5745(3) 431(5) O1 8251(2) 1483(2) 4952(2) 614(5) C5 7086(3) 298(2) 6570(2) 392(4) C6 8188(3) 1387(2) 6505(2) 415(4) C7 8225(3) 2795(2) 7212(2) 394(4) C8 7160(3) 3210(3) 8245(3) 475(5) C9 7292(3) 4570(3) 8871(3) 523(5) C (3) 5588(3) 8494(3) 489(5) C (5) 7052(3) 9205(4) 663(8) C (3) 5196(3) 7465(3) 549(6) C (3) 3822(3) 6840(3) 490(5) Table 3. Bond lengths [Å] and angles [deg] for non-hydrogen atoms. N1 C (3) C5 C (3) N1 C (3) C6 C (3) C2 Se (2) C7 C (3) C2 N (3) C7 C (3) Se1 C (4) C8 C (4) N3 C (3) C9 C (4) N3 C (3) C10 C (4) C4 O (3) C10 C (4) C4 C (3) C11 C (4) C2 N1 C (2) N1 C5 C (2) N1 C2 N (2) C5 C6 C (2) N1 C2 Se (2) C6 C7 C (2) Se1 C2 N (2) C6 C7 C (2) C2 Se1 C (1) C8 C7 C (2) C2 N3 C (2) C7 C8 C (2) C2 N3 C (2) C8 C9 C (2) C13 N3 C (2) C9 C10 C (2) N3 C4 C (2) C9 C10 C (2) N3 C4 O (2) C15 C10 C (2) O1 C4 C (2) C10 C11 C (2) N1 C5 C (2) C7 C12 C (2) C4 C5 C (2)

6 756 E. es³awska et al. The average bond angle in the five-membered ring is 108.0, agreeing well with its planarity. The bond angle C2 N1 C5, 105.1(3), is smaller than that in 2, i.e (3) (Fig. 1). Its decrease may be explained on the grounds of VSEPR theory [21] by exchange of the electron-withdrawing proton attached to N1 in 2 for the lone elctron pair in 3. The neighbouring angle N1 C2 N3, 115.3(2), is significantly greater than the corresponding one in 2, 108.0(3). This seems to be a consequence both of the sharpening of C2 N1 C5 and of the change in the substituent at C2. The selenium atom, which formed double bond with C2 in 2, has been exchanged for Se CH 3 in 3. In result, the exocyclic electron density at C2 is decreased in comparison with that in 2, which, in turn, leads to the greater opening of the bond angle N1 C2 N3. An additional effect, acting in the same direction, is the occurrence of the double bond between C2 and N1 in 3 in place of the single bond in 2. The bond angle C14 Se C2, 96.7(1), is similar to that reported for C(methyl) Se C(phenyl), i.e. 99.6(25) [22]. The bond Se CH 3 is in cis orientation in relation to C2 N1, the torsion angle N1 C2 Se C14 being 7.3(2). This causes a widening of the exocyclic angle N1 C2 Se, 125.9(2), at the cost of Se C2 N3, 118.7(2). In the six-membered ring the deviations of the endocyclic bond angles from the ideal value of 120 are in perfect agreement with those calculated from the angular parameters given in [23] for CH 3 and CH=CHR substituents in the benzene ring. The angles C5=C6 C7 and C6 C7 C8 are similar to those of the corresponding angles in 2, i.e (3) and 125.0(3), respectively [14]. They can be explained by the interplay of the requirement for planarity of the conjugated system of the rings, linked by the C5=C6 C7 bridge and a tendency to minimize repulsive interactions between N1 and H8 atoms. This system is close to planarity, as shown by the torsion angle C5=C6 C7 C8, 7.0(4), which is similar to 6.4(7), observed in the derivative 2 mentioned above [14]. The planarity in this region of molecule 3 is additionally stabilized by an intramolecular hydrogen bond C8 H8 N1 with C8 N1 = 3.100(3) Å, C8 H8 = 1.00(4) Å, H8 N1 = 2.42(4) Å and C8 H8 N1 = 125(3). The packing of the molecules in the unit cell (Fig. 3) can be best described taking into account the relatively short contacts between the five-membered ring fragments, related by the inversion centre at 0.5, 0, 0.5. In such dimers antiparallel imidazole rings are separated by about 3.5 Å. The molecular dimers interact with each other via van der Waals forces. Among them there are two short contacts between O1 and two carbon atoms, C6 and C12, at 2 x, y,1 z. These contacts, with the parameters given below, can be considered as very weak hydrogen bonds. D A D A (Å) D H (Å) H A (Å) D H A ( ) C6 O (3) 1.00(3) 2.40(3) 149(2) C12 O (3) 1.04(4) 2.46(4) 145(3)

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