Synthesis and Conformational Analysis of Sterically Congested (4R)-(−)-1-(2,4,6-Trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone: X-Ray Crystallography and Semiempirical Calculations

Al-Swaidan, Ibrahim A.; El-Azab, Adel S.; Alanazi, Amer M.; Abdel-Aziz, Alaa A.-M.

doi:https://doi.org/10.1155/2014/173902

Journal of Chemistry

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Research Article | Open Access

Volume 2014 | Article ID 173902 | https://doi.org/10.1155/2014/173902

Synthesis and Conformational Analysis of Sterically Congested (4R)-(−)-1-(2,4,6-Trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone: X-Ray Crystallography and Semiempirical Calculations

Ibrahim A. Al-Swaidan,¹Adel S. El-Azab,^1,2Amer M. Alanazi,¹and Alaa A.-M. Abdel-Aziz^1,3

Academic Editor: Fernanda Carvalho

Received02 Oct 2013

Revised04 Nov 2013

Accepted07 Nov 2013

Published05 Jan 2014

Abstract

The crystal structure of (4R)-(−)-1-(2,4,6-trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone (3) was determined by single-crystal X-ray diffraction. Compound 3 crystallizes in triclinic system in space group P1 (≠ 1). The crystal data are Å, Å, Å, , , , Å³, , g/cm³, cm⁻¹, , °C, and . The crystal structure confirmed the occurrence of three molecules of 3A, 3B, and 3C in which the n-butyryl moiety adopted the s-transoid conformation. Crystal structure also revealed that the conformation of 2,4,6-trimethylbenzenesulfonyl groups was in anti-position relative to tert-butyl group. The crystal packing showed that three molecules of compound 3 are stacked as a result of intermolecular π-π interactions between the phenyl ring of one molecule and the phenyl ring of the other molecule by approaching each other to an interplanar separation of 5.034 Å. Interestingly, these stacked molecules are also connected by intermolecular CH-π interaction. The conformational analysis of the s-transoid 3A, 3B, and 3C was separately performed by molecular mechanic MM+ force field. Additionally, computational investigation using semiempirical AM1 and PM3 methods was performed to find a correlation between experimental and calculated geometrical parameters. The data obtained suggest that the structural data furnished by the AM1 method is in better agreement with those experimentally determined for the above compound. It has been found that the lowest energetic conformer computed gives approximate correspondence with experimental solid state data.

1. Introduction

The energy based conformational searching technique is a considerable computational request and is still an active area of research. When the property of interest is energy, the following methodology is indicated: full conformational search using molecular mechanics, followed by geometry optimization using semiempirical model for selected conformers, and finally single-point calculation using ab initio models for selected conformers [1]. On the other hand, steric bulkiness of chiral 2-imidazolidinones [2] plays an effective role in greatly enhancing stereoselectivity, and so sterically congested chiral 2-imidazolidinones [3–5] represent promising auxiliaries for providing excellent diastereocontrol. We reported the synthesis and chiral application of 4-tert-butyl-2-imidazolidinone which were greatly enhanced by the occurrence of N-arylsulfonyl fragments [4]. Moreover, several 2-imidazolidinone derivatives containing diarylsulfonylurea pharmacophore have been synthesized and screened for antitumor activity against various human solid tumors [6–17]. More interestingly the structure of the arylsulfonyl-2-imidazolidinone such as 4-benzamido-3-methyl-1-tosyl-2-imidazolidinone and (S)-(+)-1-[1-(4-aminobenzoyl) indoline-5-sulfonyl]-4-phenyl-4,5-dihydroimidazol-2-one has elucidated using X-ray analysis [18, 19]. Recently, we reported about the X-ray analysis and computational studies of trans-1-acetyl-4,5-di-tert-butyl-2-imidazolidinone in which the crystal unit cell showed two independent molecules connected together by two intermolecular hydrogen bonds [20].

In such a way and in continuation of our previous report [20] we studied single-crystal X-ray and the theoretical conformational analysis of (4R)-(−)-1-(2,4,6-trimethylbenzenesulfonyl)-3-butyryl-4-tert-butyl-2-imidazolidinone (3), as a cyclic arylsulfonylurea, focusing on the configuration of substituents around the 2-imidazolidinone core and to establish the factors that influence this configuration and if this configuration can be predicted for new substituted 2-imidazolidinone.

2. Experimental

2.1. Procedure for Synthesis of (4R)-(−)-1-(2,4,6-Trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone (3)

n-Butyl lithium (1.5 M in hexane, 0.5 mmoL) was added to a stirred solution of compound 2 (0.5 mmoL) in THF (10 mL) at −78°C under nitrogen atmosphere for 10 min and n-butyryl chloride (1.0 mmoL) was added dropwise at −78°C. The reaction mixture was stirred at room temperature for 1 h and then was quenched by passing through silica gel (EtOAc, 100 mL), evaporated under vacuum, followed by column chromatography on silica gel (EtOAc: hexane) to afford compound 3 in quantitative yield.

Compound (4R)-3 (97%): white crystals, mp 125–127°C (Hexane), IR (KBr) , 1736, 1701 (CO), 1320, 1175 (); (c 1.00, CHCl₃); ¹H-NMR (CDCl₃, 500 MHz): δ 6.99 (s, 2H), 4.42–4.40 (d, 1H, ), 3.97–3.96 (d, 1H, ), 3.85–3.81 (t, 1H, ), 2.85–2.81 (m, 1H), 2.74–2.67 (m, 1H), 2.65 (s, 6H), 2.31 (s, 3H), 1.66–1.58 (m, 2H), 0.93 (s, 9H), and 0.92–0.88 (t, 3H, ).

2.2. X-Ray Data Collection, Structure Solution, and Refinement for (4R)-(−)-1-(2,4,6-Trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone (3)

2.2.1. Data Collection

(4R)-(-)-1-(2,4,6-Trimethylbenzenesulfonyl)-3-butyryl-4-tert-butyl-2-imidazolidinone (3) (Scheme 1) was prepared according to our previous report [4, 21]. A colorless plate crystal of C₂₀H₃₀N₂O₄S having approximate dimensions of 0.25 × 0.10 × 0.25 mm was mounted on a glass fiber. All measurements were made on a Rigaku AFC7R diffractometer with graphite monochromated Cu-Kα radiation and a rotating anode generator. Cell constants and orientation matrix for data collection obtained from a least-squares refinement using the setting angles of 25° carefully centered reflections in the range 59.17° < 2θ < 59.87° corresponded to a triclinic cell (Table 1).

The data were collected at a temperature of °C using the scan technique to a maximum value of 120.1°. Omega scans of several intense reflections, made prior to data collection, had an average width at half-height of 0.28° with a take-off angle of 6.0°. Scans of were made at a speed of 16.0°/min (in omega). The weak reflections (σ ()) were rescanned (maximum of 5 scans) and the counts were accumulated to ensure good counting statistics. Stationary background counts were recorded on each side of the reflection. The ratio of peak counting time to background counting time was 2 : 1. The diameter of the incident beam collimator was 0.5 mm and the crystal to detector distance was 235 mm. The computer-controlled slits were set to 3.0 mm (horizontal) and 3.0 mm (vertical).

2.2.2. Data Reduction

Of the 4942 reflections which were collected, 4649 were unique (); equivalent reflections were merged. The intensities of three representative reflections were measured after every 150 reflections. The linear absorption coefficient, , for Cu-Kα radiation is 16.0 cm⁻¹ and an empirical absorption correction based on azimuthal scans of several reflections was applied which resulted in transmission factors ranging from 0.81 to 1.00. The data were corrected for Lorentz and polarization effects and a correction for secondary extinction were applied ().

2.2.3. Structure Solution and Refinement

The structure was solved by direct methods [22] and expanded using Fourier techniques [23]. The nonhydrogen atoms were refined anisotropically and hydrogen atoms were included but not refined. The final cycle of full-matrix least-squares refinement (Least-squares: function minimized: , where and . based on counting, ) was based on 4409 observed reflections ( ()) and 729 variable parameters and converged (largest parameter shift was 0.09 times its esd) with unweighted and weighted agreement factors of

The standard deviation of an observation of unit weight (standard deviation of an observation of unit weight: , where: of observations and of variables) was 1.26 and the weighting scheme was based on counting statistics and included a factor () to down-weight the intense reflections. Plots of versus , reflection order in data collection, sin , and various classes of indices showed no unusual trends. The maximum and minimum peaks on the final difference Fourier map corresponded to 0.15 and −0.20 , respectively.

Neutral atom scattering factors were taken from Cromer and Waber [24] and anomalous dispersion effects were included in Fcalc [25]; the values for and were those of Creagh and McAuley [26]. The values for the mass attenuation coefficients are those of Creagh and McAuley [26]. All calculations were performed using the teXsan [27] crystallographic software package of Molecular Structure Corporation and crystal data summary is given in Table 1. The selected bond lengths, angles, and torsion angles are given in Tables 2–4 and the molecular structure with the atom-numbering scheme and the packing within the cell lattice are shown in Figures 1 and 3, respectively.

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(b)

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2.3. Computational Calculations

All molecular modeling calculations were performed using HyperChem version 8.0.6 [28], running on “Windows Vista” operating system installed on an Intel core 2 duo PC with a 2.66 GHz processor and 2000 Mb RAM.

2.3.1. Conformational Search

Conformational analyses of isolated molecule 3 (3A, 3B, and 3C) were done in the same way using the procedure which is suggested for conformational flexible compounds when the property of interest is energy [1]. Initial X-ray structures for the molecules 3A, 3B and 3C were used for conformational analysis with HyperChem 8.0 [28]. The MM+ [29] (calculations in vacuum, bond dipole option for electrostatics, and RMS gradient of 0.01 kcal/mol) conformational searching in torsional space was performed using the multiconformer method [30, 31]. Each molecule 3A, 3B, and 3C was subjected to a separate conformational search and the most stable conformer was energy minimized using semiempirical MO methods AM1 [32] and PM3 [33] included in MOPAC version 2009 [34] using HyperChem as GUI. Vibration frequencies calculation for each conformer was characterized to be the stable structure (no imaginary frequencies).

3. Results and Discussion

As a result of the potential conformational flexibility of the substituent groups of compound 3, we have used solid state molecular structures (as obtained from single crystal X-ray diffraction analysis) to obtain realistic structure as starting geometries for the quantum chemical calculations. Additionally, the data obtained by X-ray diffraction analysis shed light on some interesting features of its molecular structures. Some structural characteristics of compound 3 are the geometrical parameters around the ring nitrogen atoms such as the relative orientation of the n-butyryl and the 2,4,6-trimethylbenzenesulfonyl groups at N1 and N2 positions. Although, the preferred conformation in the solid phase can be different from the solution structure and in gas phase, the X-ray diffraction data are useful for comparative purposes. Overall, the combination of experimental and computational results can help in understanding the physical and chemical properties of this molecule.

3.1. X-Ray Crystal Structure of (4R)-(−)-1-(2,4,6-Trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone (3)

The molecular solid state structure of 3 and numbering system are indicated in Figure 1. Geometrical parameters for compound 3 are collected in Tables 2–4. In the crystal structure, compound 3 crystallizes in the space group (Table 1) and exists in three independent conformationally different molecules in the unit cell (3A, 3B, and 3C; see Figures 1, 2, and 3). Recently, crystal structures having more than one molecule in the unit cell have aroused interest, since these compounds can help in understanding the interactions responsible for packing as well as to guide the design of technologically useful materials [35]. The three molecules present, certain disorder in the core 2-imidazolidinone and the substituents linked to such ring. Thus, there is some ambiguity in the atomic positions of the 2-imidazolidinone skeleton, tert-butyl, -butyryl, and 2,4,6-trimethylbenzenesulfonyl groups of three molecules: 3A, 3B, and 3C. These disorders are expected due to the conformational flexibility of the tert-butyl, n-butyryl, and 2,4,6-trimethylbenzenesulfonyl moieties. The five-membered imidazolidinone ring assumes distorted envelope conformation (half-chair;LISLOO) which may be related to angle strain (angle strain is calculated as the difference between the internal angle and the ideal angle of 109.5°) [36]. Atoms system ∠N2–C3–C2 of 3A, 3B, and 3C are deviated from ideal angle by 6.2°, 6.8°, and 7.3°, respectively. Similarly ∠C3–C2–N1 system of 3A, 3B, and 3C deviates by 8.5°, 7.9°, and 7.8°, respectively, from the ideal value [17, 18, 20, 36–41]. The same pattern was observed with angle system ∠N2–C2–N2. The structures of 3A, 3B, and 3C depicted in Figures 1–3 are those more likely on the basis of standard bond distances and angles [17, 18, 20, 41]. In the three molecules (3A, 3B and 3C), the geometrical parameters of the 2-imidazolidinone ring are quite similar with few distortions (Tables 2–4). The geometries of ∠C4–N1–C2 and ∠C4–N1–C1 atoms are almost planar rather than the most stable pyramidal form with bond angles of ca. 120°–126° for the three molecules 3A, 3B, and 3C. Similarly the geometries of ∠S1–N2–C1 and ∠S1–N2–C3 are also planar with bond angles ca. as 122.1° (3A), 122.6° (3B), 121.7° (3C), 124.5° (3A and 3B), and 125.4° (3C), respectively [17, 18, 20, 38–41]. This geometry makes the two nitrogen atoms in each molecule distinguishable from a geometrical point of view. Moreover, the planarity angle ∠N2–C1–N1–C4 of molecules 3A, 3B, and 3C was deviated from the planar urea form by 23°–26° with ca −154.1°, −150.9°, and −157.1°, respectively [20, 41–44]. It must be indicated that the two nitrogen atoms in each molecules occupy anti-positions relative to the mean plane of the ring system. This anti-position of both nitrogen atoms in each molecule is one of the reasons which make the central ring nonplanar [20]. This distortion leads to trans-geometry of n-butyryl fragment around one nitrogen atom and the sulfonyl moiety of the other nitrogen atom. As expected from the previous results [20], as a result of electron distribution, flexibility, and steric congestion of the system, the 2-imidazolidinone rings in 3A, 3B, and 3C were nonplanar and adopted distorted envelope conformation (half-chair; LISLOO). A common characteristic molecules 3A, 3B, and 3C is the dihedral angle between tert-butyl and the 2-imidazolidinone rings, with values of −74.0° (3A), −67.5° (3B), and −73.5° (3C) [20, 43–46]. Similarly the dihedral angle between n-butyryl group and the 2-imidazolidinone rings is −9.6.0° (3A), −6.1° (3B), and −7.8° (3C) as expected in order to minimize unfavourable steric interactions between tert-butyl and n-butyryl moiety. Another common feature of the three molecules is the relative orientation of the n-butyryl. They adopt a transoid conformation and each n-butyryl group is nearly out of the plane of the corresponding 2-imidazolidinone (dihedral angles 6°~9°). A remarkable structural feature of the solid-state structures of molecules 3A, 3B, and 3C is the bond angles, whereas the geometrical distortion is manifested in the smaller ∠C2–C3–N2 (102.2°) and ∠N1–C2–C3 (101.0°) bond angles (Figure 1, Table 3) [20, 38–41]. In addition, the structures of molecules 3A, 3B, and 3C were superimposed in order to reveal the conformational differences of the three molecules (Figure 2). The strategy of overlay fit to match 2-imidazolidinone rings and examines any spatial differences between the atoms of the peripheral fragments. The results show that atoms of the n-butyryl, and 2,4,6-trimethylphenylsulfonyl groups occupy different spatial positions relative to the plane of 2-imidazolidinone ring which may explain the existence of such three molecules in one unit cell.

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(b)

To conclude, it is found that the solid state conformations of the three molecules of 3 (3A, 3B, and 3C) in the unit cell are quite similar, showing minor differences in some bond length and bond angle and major differences in some torsion angles at the peripheral substitution. However, and despite the high congestion in the molecular structures of these compounds, they form quiet molecular packing that likely reflects the subtle influence of the diverse intermolecular interactions.

The crystal packing of 3 is indicated in Figure 3. The molecules are arranged in a layer constituted by three molecules of 3A, 3B, and 3C and that are maintained by numbers of CH-O, CH-π, and π-π interactions [45–47]. The main structural feature of the packing of 3 is that two molecules are quite parallel to each other and connected by π-π interactions of the two aryl fragments (5.03 Å) with coordinates −4.250, −2.462, and −0.875, while the third molecule was arranged in a lateral arrangement and approximately in opposite direction to the other two molecules. Additionally, the intramolecular interactions within each molecules of 3 involve O atom of sulfonyl fragment and hydrogen atoms from the CH₃ of 2,4,6-trimethylphenyl group (1.902–2.081 Å). The main putative interactions CH-O, as inferred by relatively short distances and suitable orientations, are indicated in Figure 3. On the basis of the short distances and the wide angle, the CH-O intermolecular interactions are likely to be quite strong and an important factor to determine the crystal packing; these bonds can be considered as nonclassical hydrogen bonds [45–47] involving CH as H-bond donors. Moreover, the third opposite molecule was showing CH-π interaction of the alkyl part of the butyryl moiety of this molecule and the aromatic fragment of the middle molecule (3.86 Å). Similarly the CH₃ group of the 2,4,6-trimethylbenzenesulfonyl group of the middle molecule interacted with aromatic moiety of the third opposite lateral molecule through CH-π interaction (3.60 Å). Finally, it must be indicated that the relative orientation between two parallel molecules of 3 in the crystal packing and the third opposite lateral molecule might indicate, besides steric suitability, a tendency to minimize the polarity of the crystal (compensating the dipole moments of the molecules) [48].

3.2. Computational Studies

Despite the interesting properties of the 1-arenesulfonyl-2-imidazolidinones, these compounds have been scarcely studied from a computational point of view [20, 49, 50]. Our goal was to compute quantum-chemical derived properties that would be useful as starting points for understanding the properties of this type of ring system. Moreover, the other main task of conformational analyses of isolated molecules 3A, 3B, and 3C was to examine the stable conformations and a global energy minimum for each molecule. If there was considerable energy difference between the lowest energy of 3A, 3B, and 3C type of conformer, then we concluded that theoretical calculations predicted one type of geometric molecule. Since, the size and the variety of heteroatoms in the 2-imidazolidinones are considerable, a full semiempirical geometrical optimization is computationally very demanding. This work is simplified, if we use a realistic structure as starting geometry for the MM conformational search and quantum-chemical calculation. Therefore, the structures obtained by X-ray diffraction analysis are suitable to this end. Since compound 3 appears as three independent molecules in the asymmetric unit, the three structures (molecules 3A, 3B, and 3C) were separately submitted to the conformational search using molecular mechanic MM+ and the energy minima conformer together with the highest energy conformer were subjected to full semiempirical AM1 and PM3 geometry optimization (Figures 4 and 5). Each conformer was confirmed as minimum or transition state on the basis of frequency calculation using AM1 results.

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(b)

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3.2.1. Theoretical Calculations

Taking into account our interest in the structural study of 2-imidazolidinone, the choice of computational methods which could reproduce the experimental data with reasonable agreement was relevant. Thus, we analyzed the conformational behaviour of compound 3 using semiempirical AM1 and PM3 quantum-chemical calculations. Conformational performance of the 2-imidazolidinone 3 was examined by the rotation and orientation in the space of the flexible tert-butyl, n-butyryl and 2,4,6-trimethylbenzenesulfonyl groups. Heat of formation, relative energies and dipole moment are collected in Table 5 and characteristic torsional angles, bond angles, and bond distance are also tabulated to illustrate the final geometries obtained. For such compound 3 the MM and semiempirical calculations led to six minimum energy conformations (Figures 4 and 5) within energy differences less than 8 kcal/mol (Table 5). Additionally, the molecular structure of compound 3 was determined by MM+ and semiempirical AM1 and PM3 calculations to assess the accuracy of the theoretical methods used for compound 3. Conformations of the single molecules predicted by AM1, more than MM+ and PM3 methods, were approximately similar to that in the crystal (Figure 4).

The arrangement around the N2–S1 and N1–C4 bonds mainly determines the geometry of the N-substituent groups. Based on the geometrical comparison, these forms can be classified into two groups characterised by the torsion angle ∠C1–N1–C4–C5 denoted as conformer-A, -B, -C and -D for transoid butyryl fragment and conformer-E and -F for cisoid butyryl fragment (around −23.8° and 137.9°, resp.). For each group there are two or more possible orientations of the 2,4,6-trimethylbenzenesulfonyl moiety (torsion angle ∠C1–N2–S1–C12) with a similar energy content. However, the relative energy content of these conformers indicates a strong preference for conformations A-B, while the C-F forms are strongly destabilised. Therefore, it seems that the spatial orientations of the O=S=O of 2,4,6-trimethylbenzenesulfonyl and C=O of n-butyryl group relative to C=O of 2-imidazolidinone ring should be affecting the dipole moment as trans-orientation leads to a decrease of this force and vice versa. The high dipole moment represented by cis orientation probably due to the destabilising through-space interactions of the lone pairs of oxygen atoms yields much greater energy differences such as C-F conformations. In light of these findings, A-B conformations were more preferred compared with C-F conformations which are unfavourable and their participation may be negligible. Therefore, it seems that the orientation of n-butyryl group with 2,4,6-trimethylbenzenesulfonyl moiety exerts a significant effect on the conformational preferences of the compound 3 and this behaviour may be attributed to a combination of steric and electronic factors.

The AM1 method shows that the relative orientation of the aryl group of the most stable conformer-A is practically fixed in an anticonformation relative to position of tert-butyl fragment. These features are in concordance with the behaviour of reported molecules [17, 18]. Moreover, the aryl group can adopt two symmetric and isoenergetic conformations in which the tert-butyl and the aryl groups are syn and anti-positions (torsion angle ∠C1–N2–S1–C12 about −61.7, 61.7°). Moreover, the energy content of the three similar conformation of the conformer-A is very close with a slight predominance of the orientation of the 2,4,6-trimethylbenzenesulfonyl group as their interconversion requires a low cost (0.05 kcal/mol).

3.2.2. Comparison of the X-Ray and Calculated Structures

The crystal structure of 3 confirms the approximate behaviour of such compound in the gas phase (theoretical calculations). The good agreement between experimental torsion angles determined for 3 and those calculated for the conformer-A (Table 5) supports the correctness of the calculations. Because the barrier of energy of rotation of the three forms of conformer-A is very low so conformer-A was predicted representing all the three molecules of X-ray data. The low Gibbs energies of rotation between all possible transoid rotamers indicate the easy conversion between the three molecules in solution, and the solid state crystal structure was obtained in which it showed the important role of intermolecular interaction in stabilizing the molecules in solid states. The different disposition of the n-butyryl group (torsion angle ∠C1–N1–C4–C5 = −6.1~−9.6° in the solid state and −23.8° for the more favourable orientation computed using AM1 method) may be ascribed to the packing in the crystal structure. Similarily the different orientation of 2,4,6-trimethylbenzenesulfonyl (torsion angle ∠C1–N2–S1–C12 = −65.9°~−75.1° in the solid state and −61.7° for the most stable conformer-A may be attributed to CH-O, CH-π, and π-π interactions in the crystal packing. Owing to theoretical calculations account for very low energy differences between the three dispositions around the N2–S1 bond, their interconversion can take place easily. It was suggested that the change in the spatial orientation of the 2,4,6-trimethylbenzenesulfonyl group could be facilitated by the intermolecular interaction in the crystal structure. The anti-conformation of 2,4,6-trimethylbenzenesulfonyl adopted in the solid state relative to tert-butyl group would be more favourable for their formation due to the CH-O being sterically more accessible with lower dipole moment. These results confirm the flexibility of the 2,4,6-trimethylbenzenesulfonyl group in these 2-imidazolidinone derivatives and the strong dependence on intermolecular interactions as was previously suggested. Moreover, the great similarity between these conformers is the bond length with only 0.05 Å deviation among them. Hence, calculations at the semiempirical levels of the conformational energies of compound 3 indicate that the ideal gas-phase global energy minimum conformation is partially observed in the solid state. Rather, the effects of intermolecular interactions in the crystal structure cause the molecules to adopt higher-energy conformations, which correspond to local minima in the molecular potential energy surface. Finally to probe similarity and differences between the three-dimensional structures of the conformer-A and molecules 3A, 3B, and 3C, molecular superposition has been performed (Figure 6). The strategy of overlay fit to match 2-imidazolidinone rings and examines any spatial differences between the atoms of the 4-tert-butyl, n-butyryl, and 2,4,6-trimethylbenzenesulfonyl. The results show that atoms of the 4-tert-butyl, butyryl, and arenesulfonyl groups occupy different spatial positions relative to each other as described above.

4. Conclusion

The crystal structures of (4R)-(−)-1-(2,4,6-trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone (3) were reported. This compound 3 crystallized in layers formed by crystallographic independent molecules. These crystallographic motifs are the consequence of the interplay of the diverse intermolecular interactions in the crystal packing. The crystal packing showed three molecules of compound 3 were stacked as a result of intermolecular interaction. A computational analysis of compound 3 was performed using the MM+ force field and fully optimized with semiempirical AM1 and PM3 MO methods. The comparison of experimental versus calculated values for the selected bond lengths and angles of 3 is presented and the relative errors in calculated values are less than 3%. Both the experimental and calculated values agree that compound 3 is a sterically congested molecule. Theoretical conformational analyses have pointed out two factors that determine the conformation of the system under investigation. The first one is intermolecular interaction of the crystal packing, such as CH-O, CH-π, and π-π interactions, which stabilises and favours the occurrence of three independent molecules and the second factor is steric hindrance between substituents. The generally reasonable agreement between theoretical and experimental results have confirmed that the method which was applied for the theoretical conformational analysis of 2-imidazolidinone is good and useful for related organic molecules. Therefore, these results must be regarded as approximated and only with qualitative and comparative purposes. Moreover, the small differences between X-ray and calculated structures are consequence of different states of matter. During the theoretical calculation single isolated molecule is considered in vacuum, while many molecules are treated in solid state during X-ray diffraction. However, all the calculated geometric parameters, obtained by three used models (MM+, AM1, and PM3), represent good approximations and they can be applied as groundwork for prediction and exploring the other properties of the conformers.

5. Supporting Information Available

Crystallographic data for the structure in this paper have been deposited with the Cambridge Crystallographic Data Centre as the Supplementary Publication (no. CCDC 734938). Copies of the data can be obtained, free of charge, through application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 1223 336033 or e-mail: [email protected]).

Conflict of Interests

The author(s) declare(s) that there is no conflict of interests regarding the publication of this paper.

Acknowledgment

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding work through the research group Project no. RGP-VPP-163.

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Copyright © 2014 Ibrahim A. Al-Swaidan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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