# 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

Authors: Ibrahim A. Al-Swaidan; Adel S. El-Azab; Amer M. Alanazi; Alaa A.-M. Abdel-Aziz
Journal: Journal of Chemistry
 (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 a
=
10.6216
5 Å, b
=
16.532
1 Å, c
=
8.9572
9 Å, ∝
=
91.193
6
∘, β
=
93.849
6
∘, γ
=
88.097
4
∘, V
=
1568.2
2 Å3, Z
=
3, D
c
a
l
c
=
1.253 g/cm3, μ
CuK
α
=
15.98 cm−1, F
000
=
636.00, T
=
20.0°C, and R
=
0.037. 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.


---

## Body

## 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 usingab 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 compound2 (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) ν
max
/
cm
-
1, 1736, 1701 (CO), 1320, 1175 (S
O
2); [
α
]
D
26
=
-
12.0
° (c 1.00, CHCl3); 1H-NMR (CDCl3, 500 MHz): δ 6.99 (s, 2H), 4.42–4.40 (d, 1H, J
=
8.5
Hz), 3.97–3.96 (d, 1H, J
=
8.5
Hz), 3.85–3.81 (t, 1H, J
=
8.5
Hz), 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, J
=
7.3
Hz).


### 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).Table 1
Summary of crystal data, intensity data collection, and structure refinement for compound3 at 20.0°C.
(a)
Crystal data
Empirical formula
C20H30N2O4S
Formula weight
394.53
Crystal color, Habit
Colorless, plate
Crystal dimensions
0.25× 0.10 × 0.25 mm
Crystal system
Triclinic
Lattice type
Primitive
No. of reflections used for unit cell Determination (2θ range)
25 (59.2–59.9°)
Omega scan peak width at half-height
0.28°
Lattice parameters
a = 10.6216(5) Å
b = 16.532(1) Å
c = 8.9572(9) Å
α = 91.193(6)°
β = 93.849(6)°
γ = 88.097(4)°
V = 1568.2(2) Å3
Space group
P1 (#1)
Z value
3
D
calc
1.253 g/cm3
F
000
636.00
μ (CuKα)
15.98 cm−1
(b)
Intensity measurements
Diffractometer
Rigaku AFC7R
Radiation
CuKα (λ = 1.54178 Å)
Graphite monochromated
Attenuator
Ni foil (factor = 8.82)
Take-off angle
6.0°
Detector aperture
3.0 mm horizontal
3.0 mm vertical
Crystal to detector distance
235 mm
Voltage, current
35 kV, 150 mA
Temperature
20.0°C
Scan type
ω
-
2
θ
Scan rate
16.0°/min (inω) (up to 5 scans)
Scan Width
(1.78
+
0.30
tan
θ)°
2θ
max
120.1°
No. of reflections measured
Total: 4942
Unique: 4649 (R
int = 0.059)
(c)
Structure solution and refinement
Structure solution
Direct methods (SIR92)
Refinement
Full-matrix least-squares
P factor
0.0800
Anomalous dispersion
All nonhydrogen atoms
No. of observations(
I
>
3.00
σ
(
I
)
)
4409
No. of variables
729
Reflection/parameter ratio
6.05
Residuals:R; Rw
0.037; 0.056
ResidualsR1
0.037
No. of reflections to calcR1
4409
Goodness of fit indicator
1.26
Max shift/error in final cycle
0.09
Maximum peak in final diff. map
0.15 e−/Å3
Minimum peak in final diff. map
−0.20 e−/Å3Scheme 1
Synthesis of (4R)-(−)-1-(2,4,6-Trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone (3).The data were collected at a temperature of20
±
1°C using the ω
-
2
θ scan technique to a maximum 2
θ 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 (
1.78
+
0.30
tan
θ
)
° were made at a speed of 16.0°/min (in omega). The weak reflections (I
<
10.0
σ (I)) 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 (R
int
=
0.059); equivalent reflections were merged. The intensities of three representative reflections were measured after every 150 reflections. The linear absorption coefficient, μ, 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 (coefficient
=
6.35905
e
-
06).


#### 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: ∑
ω
(
|
Fo
|
-
|
Fc
|
)
2, where w
=
1
/
σ
2
(
Fo
)
=
[
σ
c
2
(
Fo
)
+
(
p
2
/
4
)
F
o
2
]
-
1 and σ
c
2
(
Fo
)
=
e
.
s
.
d. based on counting, p
=
p
-factor) was based on 4409 observed reflections (I
>
3.00
σ (I)) and 729 variable parameters and converged (largest parameter shift was 0.09 times its esd) with unweighted and weighted agreement factors of
(1)
R
=
∑
|
|
Fo
|
-
|
Fc
|
|
∑
|
Fo
|
=
0.037
,
R
ω
=
∑
ω
(
|
Fo
|
-
|
Fc
|
)
2
∑
ω
F
o
2
=
0.056
.The standard deviation of an observation of unit weight (standard deviation of an observation of unit weight:∑
ω
(
|
Fo
|
-
|
Fc
|
)
2
/
(
No
-
Nv
), where: no
.
=
number of observations and nv
=
number of variables) was 1.26 and the weighting scheme was based on counting statistics and included a factor (P
=
0.080) to down-weight the intense reflections. Plots of ∑
ω
(
|
Fo
|
-
|
Fc
|
)
2 versus |
Fo
|, reflection order in data collection, sin θ
/
λ, 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 e
-
/
Å
3, respectively.Neutral atom scattering factors were taken from Cromer and Waber [24] and anomalous dispersion effects were included in Fcalc [25]; the values for Δ
f
′ and Δ
f
′
′ 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.Table 2
Experimental bond lengths (Å).
Atom
Atom
Distance
Atom
Atom
Distance
S1A
O3A
1.416(3)
S1A
O4A
1.428(3)
S1A
N2A
1.671(3)
S1A
C12A
1.777(4)
S1B
O3B
1.430(4)
S1B
O4B
1.421(4)
S1B
N2B
1.664(3)
S1B
C12B
1.773(4)
S1C
O3C
1.416(3)
S1C
O4C
1.425(3)
S1C
N2C
1.669(3)
S1C
C12C
1.768(4)
O1A
C4A
1.215(5)
O1B
C4B
1.219(5)
O1C
C4C
1.210(5)
O2A
C1A
1.200(4)
O2B
C1B
1.209(5)
O2C
C1C
1.203(5)
N1A
C1A
1.376(5)
N1A
C2A
1.485(5)
N1A
C4A
1.408(5)
N1B
C1B
1.380(5)
N1B
C2B
1.485(5)
N1B
C4B
1.401(5)
N1C
C1C
1.386(5)
N1C
C2C
1.476(5)
N1C
C4C
1.413(5)
N2A
C1A
1.395(5)
N2A
C3A
1.469(5)
N2B
C1B
1.386(5)
N2B
C3B
1.473(5)
N2C
C1C
1.386(5)
N2C
C3C
1.486(5)
C2A
C3A
1.523(5)
C2A
C8A
1.556(6)
C2B
C3B
1.531(5)
C2B
C8B
1.549(5)
C2C
C3C
1.520(5)
C2C
C8C
1.550(5)
C4A
C5A
1.507(6)
C4B
C5B
1.503(6)
C4C
C5C
1.486(6)
C5A
C6A
1.531(6)
C5B
C6B
1.507(7)
C5C
C6C
1.516(6)
C6A
C7A
1.490(8)
C6B
C7B
1.476(9)
C6C
C7C
1.492(9)
C8A
C9A
1.533(7)
C8A
C10A
1.533(6)
C8A
C11A
1.502(7)
C8B
C9B
1.515(7)
C8B
C10B
1.530(6)
C8B
C11B
1.508(7)
C8C
C9C
1.515(8)
C8C
C10C
1.523(6)
C8C
C11C
1.532(7)
C12A
C13A
1.401(5)
C12A
C17A
1.411(6)
C12B
C13B
1.412(6)
C12B
C17B
1.407(6)
C12C
C13C
1.410(6)
C12C
C17C
1.403(6)
C13A
C14A
1.383(6)
C13A
C18A
1.502(6)
C13B
C14B
1.408(7)
C13B
C18B
1.487(7)
C13C
C14C
1.404(6)
C13C
C18C
1.502(6)
C14A
C15A
1.377(6)
C14B
C15B
1.372(7)
C14C
C15C
1.355(7)
C15A
C16A
1.363(6)
C15A
C19A
1.500(6)
C15B
C16B
1.376(7)
C15B
C19B
1.507(8)
C15C
C16C
1.368(7)
C15C
C19C
1.503(7)
C16A
C17A
1.396(6)
C16B
C17B
1.392(7)
C16C
C17C
1.404(6)
C17A
C20A
1.500(6)
C17B
C20B
1.506(7)
C17C
C20C
1.506(6)Table 3
Experimental bond angles (deg).
Atom
Atom
Atom
Angle
Atom
Atom
Atom
Angle
O3A
S1A
O4A
118.5(2)
O3A
S1A
N2A
108.4(2)
O3A
S1A
C12A
110.8(2)
O4A
S1A
N2A
102.9(2)
O4A
S1A
C12A
110.6(2)
N2A
S1A
C12A
104.3(2)
O3B
S1B
O4B
117.6(2)
O3B
S1B
N2B
103.7(2)
O3B
S1B
C12B
110.8(2)
O4B
S1B
N2B
108.8(2)
O4B
S1B
C12B
110.5(2)
N2B
S1B
C12B
104.3(2)
O3C
S1C
O4C
118.2(2)
O3C
S1C
N2C
107.7(2)
O3C
S1C
C12C
110.1(2)
O4C
S1C
N2C
103.9(2)
O4C
S1C
C12C
111.2(2)
N2C
S1C
C12C
104.7(2)
C1A
N1A
C2A
111.9(3)
C1A
N1A
C4A
126.2(3)
C2A
N1A
C4A
120.4(3)
C1B
N1B
C2B
111.0(3)
C1A
N1B
C4B
126.4(3)
C2B
N1B
C4B
120.5(3)
C1C
N1C
C2C
111.7(3)
C1C
N1C
C4C
126.4(3)
C2C
N1C
C4C
120.5(3)
S1A
N2A
C1A
122.1(2)
S1A
N2A
C3A
124.5(2)
C1A
N2A
C3A
111.1(3)
S1B
N2B
C1B
122.6(3)
S1B
N2B
C3B
124.5(3)
C1B
N2B
C3B
111.3(3)
S1C
N2C
C1C
121.7(3)
S1C
N2C
C3C
125.4(3)
C1C
N2C
C3C
111.0(3)
O2A
C1A
N1A
128.9(3)
O2A
C1A
N2A
124.4(3)
N1A
C1A
N2A
106.7(3)
O2B
C1B
N1B
127.9(4)
O2B
C1B
N2B
124.7(4)
N1B
C1B
N2B
107.4(3)
O2C
C1C
N1C
128.0(4)
O2C
C1C
N2C
125.4(4)
N1C
C1C
N2C
106.6(3)
N1A
C2A
C3A
101.0(3)
N1A
C2A
C8A
113.5(3)
C3A
C2A
C8A
113.2(3)
N1B
C2B
C3B
101.6(3)
N1B
C2B
C8B
113.8(3)
C3B
C2B
C8B
114.6(3)
N1C
C2C
C3C
101.7(3)
N1C
C2C
C8C
114.6(3)
C3C
C2C
C8C
113.4(3)
N2A
C3A
C2A
103.3(3)
N2B
C3B
C2B
102.7(3)
N2C
C3C
C2C
102.2(3)
O1A
C4A
N1A
119.0(4)
O1A
C4A
C5A
122.7(4)
N1A
C4A
C5A
118.2(3)
O1B
C4B
N1B
119.1(4)
O1B
C4B
C5B
122.4(4)
N1B
C4B
C5B
118.4(3)
O1C
C4C
N1C
118.1(4)
O1C
C4C
C5C
123.5(4)
N1C
C4C
C5C
118.4(3)
C4A
C5A
C6A
111.4(4)
C4B
C5B
C6B
112.3(4)
C4C
C5C
C6C
112.5(4)
C5A
C6A
C7A
111.6(4)
C5B
C6B
C7B
112.3(5)
C5C
C6C
C7C
112.9(4)
C2A
C8A
C9A
110.3(4)
C2A
C8A
C10A
106.3(4)
C2A
C8A
C11A
113.9(3)
C9A
C8A
C10A
108.2(4)
C9A
C8A
C11A
108.0(5)
C10A
C8A
C11A
110.1(4)
C2B
C8B
C9B
110.9(3)
C2B
C8B
C10B
106.3(4)
C2B
C8B
C11B
112.0(3)
C9B
C8B
C10B
109.9(4)
C9B
C8B
C11B
107.9(4)
C10B
C8B
C11B
109.8(4)
C2C
C8C
C9C
110.8(4)
C2C
C8C
C10C
107.4(3)
C2C
C8C
C11C
111.8(3)
C9C
C8C
C10C
108.5(4)
C9C
C8C
C11C
108.6(5)
C10C
C8C
C11C
109.7(4)
S1A
C12A
C13A
118.1(3)
S1A
C12A
C17A
120.4(3)
C13A
C12A
C17A
121.4(4)
S1B
C12B
C13B
120.3(3)
S1B
C12B
C17B
118.3(3)
C13B
C128
C17B
121.3(4)
S1C
C12C
C13C
118.4(3)
S1C
C12C
C17C
120.7(3)
C13C
C12C
C17C
120.8(4)
C12A
C13A
C14A
117.5(4)
C12A
C13A
C18A
125.7(4)
C14A
C13A
C18A
116.8(4)
C12B
C13B
C14B
117.2(4)
C12B
C13B
C18B
127.2(4)
C14B
C13B
C18B
115.6(4)
C12C
C13C
C14C
117.8(4)
C12C
C13C
C18C
125.2(4)
C14C
C13C
C18C
117.0(4)
C13A
C14A
C15A
122.9(4)
C13B
C14B
C15B
122.4(4)
C13C
C14C
C15C
122.3(4)
C14A
C15A
C16A
118.2(4)
C14A
C15A
C19A
121.1(4)
C16A
C15A
C19A
120.6(4)
C14B
C15B
C16B
118.6(4)
C14B
C15B
C19B
120.2(5)
C16B
C15B
C19B
121.2(5)
C14C
C15C
C16C
118.9(4)
C14C
C15C
C19C
121.5(5)
C16C
C15C
C19C
119.6(4)
C15A
C16A
C17A
123.1(4)
C15B
C16B
C17B
122.8(4)
C15C
C16C
C17C
122.8(4)
C12A
C17A
C16A
116.8(4)
C12A
C17A
C20A
126.3(4)
C16A
C17A
C20A
116.9(4)
C12B
C17B
C16B
117.6(4)
C12B
C17B
C20B
125.4(4)
C16B
C17B
C20B
117.0(4)
C12C
C17C
C16C
117.2(4)
C12C
C17C
C20C
126.7(4)
C16C
C17C
C20C
116.1(4)Table 4
Experimental dihedral angles (deg).
Atom
Atom
Atom
Atom
Angle
Atom
Atom
Atom
Atom
Angle
S1A
N2A
C1A
O2A
20.7(5)
S1A
N2A
C1A
N1A
−158.4(2)
S1A
N2A
C3A
C2A
144.3(3)
S1A
C12A
C13A
C14A
174.9(3)
S1A
C12A
C13A
C18A
−4.1(5)
S1A
C12A
C17A
C16A
−175.1(3)
S1A
C12A
C17A
C20A
5.4(6)
S1B
N2B
C1B
O2B
17.4(5)
S1B
N2B
C1B
N1B
−162.1(3)
S1B
N2B
C3B
C2B
148.0(3)
S1B
C12B
C13B
C14B
−178.1(3)
S1B
C12B
C13B
C18B
2.7(6)
S1B
C12B
C17B
C16B
177.0(3)
S1B
C12B
C17B
C20B
−3.4(5)
S1C
N2C
C1C
O2C
23.1(6)
S1C
N2C
C1C
N1C
−156.5(3)
S1C
N2C
C3C
C2C
142.4(3)
S1C
C12C
C13C
C14C
175.0(3)
S1C
C12C
C13C
C18C
−5.3(6)
S1C
C12C
C17C
C16C
−173.8(3)
S1C
C12C
C17C
C20C
5.8(6)
O1A
C4A
N1A
C1A
167.1(4)
O1A
C4A
N1A
C2A
2.6(6)
O1A
C4A
C5A
C6A
0.1(6)
O1B
C4B
N1B
C1B
170.5(4)
O1B
C4B
N1B
C2B
8.5(5)
O1B
C4B
C5B
C6B
−13.6(6)
O1C
C4C
N1C
C1C
170.2(4)
O1C
C4C
N1C
C2C
4.7(6)
O1C
C4C
C5C
C6C
4.0(7)
O2A
C1A
N1A
C2A
−167.5(4)
O2A
C1A
N1A
C4A
26.8(6)
O2A
C1A
N2A
C3A
−175.7(4)
O2B
C1B
N1B
C2B
−167.0(4)
O2B
C1B
N1B
C4B
29.6(6)
O2B
C1B
N2B
C3B
−176.3(4)
O2C
C1C
N1C
C2C
−170.1(4)
O2C
C1C
N1C
C4C
23.3(6)
O2C
C1C
N2C
C3C
−171.9(4)
O3A
S1A
N2A
C1A
48.6(3)
O3A
S1A
N2A
C3A
−112.6(3)
O3A
S1A
C12A
C13A
171.4(3)
O3A
S1A
C12A
C17A
−10.7(4)
O3B
S1B
N2B
C1B
178.1(3)
O3B
S1B
N2B
C3B
13.6(4)
O3B
S1B
C12B
C13B
−142.5(3)
O3B
S1B
C12B
C17B
38.3(3)
O3C
S1C
N2C
C1C
42.0(3)
O3C
S1C
N2C
C3C
−120.7(3)
O3C
S1C
C12C
C13C
170.4(3)
O3C
S1C
C12C
C17C
−12.7(4)
O4A
S1A
N2A
C1A
174.9(3)
O4A
S1A
N2A
C3A
13.6(4)
O4A
S1A
C12A
C13A
38.0(3)
O4A
S1A
C12A
C17A
−144.1(3)
O4B
S1B
N2B
C1B
52.1(4)
O4B
S1B
N2B
C3B
−112.4(3)
O4B
S1B
C12B
C13B
−10.3(4)
O4B
S1B
C12B
C17B
170.5(3)
O4C
S1C
N2C
C1C
168.2(3)
O4C
S1C
N2C
C3C
5.4(4)
O4C
S1C
C12C
C13C
37.5(4)
O4C
S1C
C12C
C17C
−145.6(3)
N1A
C1A
N2A
C3A
5.2(4)
N1A
C2A
C3A
N2A
23.3(4)
N1A
C2A
C8A
C9A
54.5(5)
N1A
C2A
C8A
C10A
171.6(4)
N1A
C2A
C8A
C11A
−67.1(5)
N1A
C4A
C5A
C6A
176.7(4)
N1B
C1B
N2B
C3B
4.2(4)
N1B
C2B
C3B
N2B
23.2(4)
N1B
C2B
C8B
C9B
56.9(5)
N1B
C2B
C8B
C10B
176.3(4)
N1B
C2B
C8B
C11B
−63.7(5)
N1B
C4B
C5B
C6B
162.9(4)
N1C
C1C
N2C
C3C
8.5(4)
N1C
C2C
C3C
N2C
25.1(4)
N1C
C2C
C8C
C9C
52.0(5)
N1C
C2C
C8C
C10C
170.3(4)
N1C
C2C
C8C
C11C
−69.3(5)
N1C
C4C
C5C
C6C
−178.1(4)
N2A
S1A
C12A
C13A
−72.1(3)
N2A
S1A
C12A
C17A
105.8(3)
N2A
C1A
N1A
C2A
11.6(4)
N2A
C1A
N1A
C4A
−154.1(4)
N2A
C3A
C2A
C8A
−98.4(4)
N2B
S1B
C12B
C13B
106.4(3)
N2B
S1B
C12B
C17B
−72.7(3)
N2B
C1B
N1B
C2B
12.4(4)
N2B
C1B
N1B
C4B
−150.9(3)
N2B
C3B
C2B
C8B
−99.9(4)
N2C
S1C
C12C
C13C
−74.1(3)
N2C
S1C
C12C
C17C
102.9(3)
N2C
C1C
N1C
C2C
9.5(4)
N2C
C1C
N1C
C4C
−157.1(3)
N2C
C3C
C2C
C8C
−98.5(3)
C1A
N1A
C2A
C3A
−22.4(4)
C1A
N1A
C2A
C8A
99.1(4)
C1A
N1A
C4A
C5A
−9.6(6)
C1A
N2A
S1A
C12A
−69.5(3)
C1A
N2A
C3A
C2A
−18.8(4)
C1B
N1B
C2B
C3B
−22.8(4)
C1B
N1B
C2B
C8B
100.9(4)
C1B
N1B
C4B
C5B
−6.1(6)
C1B
N2B
S1B
C12B
−65.9(3)
C1B
N2B
C3B
C2B
−18.0(4)
C1C
N1C
C2C
C3C
−22.5(4)
C1C
N1C
C2C
C8C
100.3(4)
C1C
N1C
C4C
C5C
−7.8(6)
C1C
N2C
S1C
C12C
−75.1(3)
C1C
N2C
C3C
C2C
−21.9(4)
C2A
N1A
C4A
C5A
−174.2(3)
C2B
N1B
C4B
C5B
−168.1(3)
C2C
N1C
C4C
C5C
−173.4(4)
C3A
N2A
S1A
C12A
129.3(3)
C3A
C2A
N1A
C4A
144.2(3)
C3A
C2A
C8A
C9A
168.9(4)
C3A
C2A
C8A
C10A
−74.0(4)
C3A
C2A
C8A
C11A
47.3(5)
C3B
N2B
S1B
C12B
129.6(6)
C3B
C2B
N1B
C4B
141.7(3)
C3B
C2B
C8B
C19B
173.2(4)
C3B
C2B
C8B
C10B
−67.5(5)
C3B
C2B
C8B
C11B
52.5(5)
C3C
N2C
S1C
C12C
122.1(3)
C3C
C2C
N1C
C4C
145.0(3)
C3C
C2C
C8C
C9C
168.1(4)
C3C
C2C
C8C
C10C
−73.5(4)
C3C
C2C
C8C
C11C
46.9(5)
C4A
N1A
C2A
C8A
−94.3(4)
C4A
C5A
C6A
C7A
−173.9(4)
C4B
N1B
C2B
C8B
−94.7(4)
C4B
C5B
C6B
C7B
−173.8(5)
C4C
N1C
C2C
C8C
−92.3(4)
C4C
C5C
C6C
C7C
−173.4(5)
C12A
C13A
C14A
C15A
0.6(6)
C12A
C17A
C16A
C15A
−0.2(6)
C12B
C13B
C14B
C15B
1.3(6)
C12B
C17B
C16B
C15B
1.2(6)
C12C
C13C
C14C
C15C
−1.5(6)
C12C
C17C
C16C
C15C
−0.9(6)
C13A
C12A
C17A
C16A
2.7(5)
C13A
C12A
C17A
C20A
−176.8(4)
C13A
C14A
C15A
C16A
1.8(6)
C13A
C14A
C15A
C19A
−175.9(4)
C13B
C12B
C17B
C16B
−2.2(5)
C13B
C12B
C17B
C20B
177.4(4)
C13B
C14B
C15B
C16B
−2.3(6)
C13B
C14B
C15B
C19B
177.4(5)
C13C
C12C
C17C
C16C
3.0(6)
C13C
C12C
C17C
C20C
−177.4(4)
C13C
C14C
C15C
C16C
3.7(7)
C13C
C14C
C15C
C19C
−175.2(4)
C14A
C13A
C12A
C17A
−3.0(5)
C14A
C15A
C16A
C17A
−2.0(6)
C14B
C13B
C12B
C17B
1.0(5)
C14B
C15B
C16B
C17B
1.0(7)
C14C
C13C
C12C
C17C
1.9(6)
C14C
C15C
C16C
C17C
−2.4(7)
C15A
C14A
C13A
C18A
179.8(4)
C15A
C16A
C17A
C20A
179.4(4)
C15B
C14B
C13B
C18B
−179.4(4)
C15B
C16B
C17B
C20B
−178.5(4)
C15C
C14C
C13C
C18C
178.8(4)
C15C
C16C
C17C
C20C
179.5(4)
C17A
C12A
C13A
C18A
178.0(4)
C17A
C16A
C15A
C19A
175.6(4)
C17B
C12B
C13B
C18B
−178.2(4)
C17B
C16B
C15B
C19B
−178.7(4)
C17C
C12C
C13C
C18C
177.7(4)
C17C
C16C
C15C
C19C
176.5(4)Numbering system of the three molecules (3A; (a), 3B; (b), and 3C; (c)) of the X-ray structure of compound 3.
(a)
(b)
(c)


### 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 molecule3 (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).


## 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 compound2 (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) ν
max
/
cm
-
1, 1736, 1701 (CO), 1320, 1175 (S
O
2); [
α
]
D
26
=
-
12.0
° (c 1.00, CHCl3); 1H-NMR (CDCl3, 500 MHz): δ 6.99 (s, 2H), 4.42–4.40 (d, 1H, J
=
8.5
Hz), 3.97–3.96 (d, 1H, J
=
8.5
Hz), 3.85–3.81 (t, 1H, J
=
8.5
Hz), 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, J
=
7.3
Hz).


## 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).Table 1
Summary of crystal data, intensity data collection, and structure refinement for compound3 at 20.0°C.
(a)
Crystal data
Empirical formula
C20H30N2O4S
Formula weight
394.53
Crystal color, Habit
Colorless, plate
Crystal dimensions
0.25× 0.10 × 0.25 mm
Crystal system
Triclinic
Lattice type
Primitive
No. of reflections used for unit cell Determination (2θ range)
25 (59.2–59.9°)
Omega scan peak width at half-height
0.28°
Lattice parameters
a = 10.6216(5) Å
b = 16.532(1) Å
c = 8.9572(9) Å
α = 91.193(6)°
β = 93.849(6)°
γ = 88.097(4)°
V = 1568.2(2) Å3
Space group
P1 (#1)
Z value
3
D
calc
1.253 g/cm3
F
000
636.00
μ (CuKα)
15.98 cm−1
(b)
Intensity measurements
Diffractometer
Rigaku AFC7R
Radiation
CuKα (λ = 1.54178 Å)
Graphite monochromated
Attenuator
Ni foil (factor = 8.82)
Take-off angle
6.0°
Detector aperture
3.0 mm horizontal
3.0 mm vertical
Crystal to detector distance
235 mm
Voltage, current
35 kV, 150 mA
Temperature
20.0°C
Scan type
ω
-
2
θ
Scan rate
16.0°/min (inω) (up to 5 scans)
Scan Width
(1.78
+
0.30
tan
θ)°
2θ
max
120.1°
No. of reflections measured
Total: 4942
Unique: 4649 (R
int = 0.059)
(c)
Structure solution and refinement
Structure solution
Direct methods (SIR92)
Refinement
Full-matrix least-squares
P factor
0.0800
Anomalous dispersion
All nonhydrogen atoms
No. of observations(
I
>
3.00
σ
(
I
)
)
4409
No. of variables
729
Reflection/parameter ratio
6.05
Residuals:R; Rw
0.037; 0.056
ResidualsR1
0.037
No. of reflections to calcR1
4409
Goodness of fit indicator
1.26
Max shift/error in final cycle
0.09
Maximum peak in final diff. map
0.15 e−/Å3
Minimum peak in final diff. map
−0.20 e−/Å3Scheme 1
Synthesis of (4R)-(−)-1-(2,4,6-Trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone (3).The data were collected at a temperature of20
±
1°C using the ω
-
2
θ scan technique to a maximum 2
θ 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 (
1.78
+
0.30
tan
θ
)
° were made at a speed of 16.0°/min (in omega). The weak reflections (I
<
10.0
σ (I)) 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 (R
int
=
0.059); equivalent reflections were merged. The intensities of three representative reflections were measured after every 150 reflections. The linear absorption coefficient, μ, 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 (coefficient
=
6.35905
e
-
06).


### 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: ∑
ω
(
|
Fo
|
-
|
Fc
|
)
2, where w
=
1
/
σ
2
(
Fo
)
=
[
σ
c
2
(
Fo
)
+
(
p
2
/
4
)
F
o
2
]
-
1 and σ
c
2
(
Fo
)
=
e
.
s
.
d. based on counting, p
=
p
-factor) was based on 4409 observed reflections (I
>
3.00
σ (I)) and 729 variable parameters and converged (largest parameter shift was 0.09 times its esd) with unweighted and weighted agreement factors of
(1)
R
=
∑
|
|
Fo
|
-
|
Fc
|
|
∑
|
Fo
|
=
0.037
,
R
ω
=
∑
ω
(
|
Fo
|
-
|
Fc
|
)
2
∑
ω
F
o
2
=
0.056
.The standard deviation of an observation of unit weight (standard deviation of an observation of unit weight:∑
ω
(
|
Fo
|
-
|
Fc
|
)
2
/
(
No
-
Nv
), where: no
.
=
number of observations and nv
=
number of variables) was 1.26 and the weighting scheme was based on counting statistics and included a factor (P
=
0.080) to down-weight the intense reflections. Plots of ∑
ω
(
|
Fo
|
-
|
Fc
|
)
2 versus |
Fo
|, reflection order in data collection, sin θ
/
λ, 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 e
-
/
Å
3, respectively.Neutral atom scattering factors were taken from Cromer and Waber [24] and anomalous dispersion effects were included in Fcalc [25]; the values for Δ
f
′ and Δ
f
′
′ 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.Table 2
Experimental bond lengths (Å).
Atom
Atom
Distance
Atom
Atom
Distance
S1A
O3A
1.416(3)
S1A
O4A
1.428(3)
S1A
N2A
1.671(3)
S1A
C12A
1.777(4)
S1B
O3B
1.430(4)
S1B
O4B
1.421(4)
S1B
N2B
1.664(3)
S1B
C12B
1.773(4)
S1C
O3C
1.416(3)
S1C
O4C
1.425(3)
S1C
N2C
1.669(3)
S1C
C12C
1.768(4)
O1A
C4A
1.215(5)
O1B
C4B
1.219(5)
O1C
C4C
1.210(5)
O2A
C1A
1.200(4)
O2B
C1B
1.209(5)
O2C
C1C
1.203(5)
N1A
C1A
1.376(5)
N1A
C2A
1.485(5)
N1A
C4A
1.408(5)
N1B
C1B
1.380(5)
N1B
C2B
1.485(5)
N1B
C4B
1.401(5)
N1C
C1C
1.386(5)
N1C
C2C
1.476(5)
N1C
C4C
1.413(5)
N2A
C1A
1.395(5)
N2A
C3A
1.469(5)
N2B
C1B
1.386(5)
N2B
C3B
1.473(5)
N2C
C1C
1.386(5)
N2C
C3C
1.486(5)
C2A
C3A
1.523(5)
C2A
C8A
1.556(6)
C2B
C3B
1.531(5)
C2B
C8B
1.549(5)
C2C
C3C
1.520(5)
C2C
C8C
1.550(5)
C4A
C5A
1.507(6)
C4B
C5B
1.503(6)
C4C
C5C
1.486(6)
C5A
C6A
1.531(6)
C5B
C6B
1.507(7)
C5C
C6C
1.516(6)
C6A
C7A
1.490(8)
C6B
C7B
1.476(9)
C6C
C7C
1.492(9)
C8A
C9A
1.533(7)
C8A
C10A
1.533(6)
C8A
C11A
1.502(7)
C8B
C9B
1.515(7)
C8B
C10B
1.530(6)
C8B
C11B
1.508(7)
C8C
C9C
1.515(8)
C8C
C10C
1.523(6)
C8C
C11C
1.532(7)
C12A
C13A
1.401(5)
C12A
C17A
1.411(6)
C12B
C13B
1.412(6)
C12B
C17B
1.407(6)
C12C
C13C
1.410(6)
C12C
C17C
1.403(6)
C13A
C14A
1.383(6)
C13A
C18A
1.502(6)
C13B
C14B
1.408(7)
C13B
C18B
1.487(7)
C13C
C14C
1.404(6)
C13C
C18C
1.502(6)
C14A
C15A
1.377(6)
C14B
C15B
1.372(7)
C14C
C15C
1.355(7)
C15A
C16A
1.363(6)
C15A
C19A
1.500(6)
C15B
C16B
1.376(7)
C15B
C19B
1.507(8)
C15C
C16C
1.368(7)
C15C
C19C
1.503(7)
C16A
C17A
1.396(6)
C16B
C17B
1.392(7)
C16C
C17C
1.404(6)
C17A
C20A
1.500(6)
C17B
C20B
1.506(7)
C17C
C20C
1.506(6)Table 3
Experimental bond angles (deg).
Atom
Atom
Atom
Angle
Atom
Atom
Atom
Angle
O3A
S1A
O4A
118.5(2)
O3A
S1A
N2A
108.4(2)
O3A
S1A
C12A
110.8(2)
O4A
S1A
N2A
102.9(2)
O4A
S1A
C12A
110.6(2)
N2A
S1A
C12A
104.3(2)
O3B
S1B
O4B
117.6(2)
O3B
S1B
N2B
103.7(2)
O3B
S1B
C12B
110.8(2)
O4B
S1B
N2B
108.8(2)
O4B
S1B
C12B
110.5(2)
N2B
S1B
C12B
104.3(2)
O3C
S1C
O4C
118.2(2)
O3C
S1C
N2C
107.7(2)
O3C
S1C
C12C
110.1(2)
O4C
S1C
N2C
103.9(2)
O4C
S1C
C12C
111.2(2)
N2C
S1C
C12C
104.7(2)
C1A
N1A
C2A
111.9(3)
C1A
N1A
C4A
126.2(3)
C2A
N1A
C4A
120.4(3)
C1B
N1B
C2B
111.0(3)
C1A
N1B
C4B
126.4(3)
C2B
N1B
C4B
120.5(3)
C1C
N1C
C2C
111.7(3)
C1C
N1C
C4C
126.4(3)
C2C
N1C
C4C
120.5(3)
S1A
N2A
C1A
122.1(2)
S1A
N2A
C3A
124.5(2)
C1A
N2A
C3A
111.1(3)
S1B
N2B
C1B
122.6(3)
S1B
N2B
C3B
124.5(3)
C1B
N2B
C3B
111.3(3)
S1C
N2C
C1C
121.7(3)
S1C
N2C
C3C
125.4(3)
C1C
N2C
C3C
111.0(3)
O2A
C1A
N1A
128.9(3)
O2A
C1A
N2A
124.4(3)
N1A
C1A
N2A
106.7(3)
O2B
C1B
N1B
127.9(4)
O2B
C1B
N2B
124.7(4)
N1B
C1B
N2B
107.4(3)
O2C
C1C
N1C
128.0(4)
O2C
C1C
N2C
125.4(4)
N1C
C1C
N2C
106.6(3)
N1A
C2A
C3A
101.0(3)
N1A
C2A
C8A
113.5(3)
C3A
C2A
C8A
113.2(3)
N1B
C2B
C3B
101.6(3)
N1B
C2B
C8B
113.8(3)
C3B
C2B
C8B
114.6(3)
N1C
C2C
C3C
101.7(3)
N1C
C2C
C8C
114.6(3)
C3C
C2C
C8C
113.4(3)
N2A
C3A
C2A
103.3(3)
N2B
C3B
C2B
102.7(3)
N2C
C3C
C2C
102.2(3)
O1A
C4A
N1A
119.0(4)
O1A
C4A
C5A
122.7(4)
N1A
C4A
C5A
118.2(3)
O1B
C4B
N1B
119.1(4)
O1B
C4B
C5B
122.4(4)
N1B
C4B
C5B
118.4(3)
O1C
C4C
N1C
118.1(4)
O1C
C4C
C5C
123.5(4)
N1C
C4C
C5C
118.4(3)
C4A
C5A
C6A
111.4(4)
C4B
C5B
C6B
112.3(4)
C4C
C5C
C6C
112.5(4)
C5A
C6A
C7A
111.6(4)
C5B
C6B
C7B
112.3(5)
C5C
C6C
C7C
112.9(4)
C2A
C8A
C9A
110.3(4)
C2A
C8A
C10A
106.3(4)
C2A
C8A
C11A
113.9(3)
C9A
C8A
C10A
108.2(4)
C9A
C8A
C11A
108.0(5)
C10A
C8A
C11A
110.1(4)
C2B
C8B
C9B
110.9(3)
C2B
C8B
C10B
106.3(4)
C2B
C8B
C11B
112.0(3)
C9B
C8B
C10B
109.9(4)
C9B
C8B
C11B
107.9(4)
C10B
C8B
C11B
109.8(4)
C2C
C8C
C9C
110.8(4)
C2C
C8C
C10C
107.4(3)
C2C
C8C
C11C
111.8(3)
C9C
C8C
C10C
108.5(4)
C9C
C8C
C11C
108.6(5)
C10C
C8C
C11C
109.7(4)
S1A
C12A
C13A
118.1(3)
S1A
C12A
C17A
120.4(3)
C13A
C12A
C17A
121.4(4)
S1B
C12B
C13B
120.3(3)
S1B
C12B
C17B
118.3(3)
C13B
C128
C17B
121.3(4)
S1C
C12C
C13C
118.4(3)
S1C
C12C
C17C
120.7(3)
C13C
C12C
C17C
120.8(4)
C12A
C13A
C14A
117.5(4)
C12A
C13A
C18A
125.7(4)
C14A
C13A
C18A
116.8(4)
C12B
C13B
C14B
117.2(4)
C12B
C13B
C18B
127.2(4)
C14B
C13B
C18B
115.6(4)
C12C
C13C
C14C
117.8(4)
C12C
C13C
C18C
125.2(4)
C14C
C13C
C18C
117.0(4)
C13A
C14A
C15A
122.9(4)
C13B
C14B
C15B
122.4(4)
C13C
C14C
C15C
122.3(4)
C14A
C15A
C16A
118.2(4)
C14A
C15A
C19A
121.1(4)
C16A
C15A
C19A
120.6(4)
C14B
C15B
C16B
118.6(4)
C14B
C15B
C19B
120.2(5)
C16B
C15B
C19B
121.2(5)
C14C
C15C
C16C
118.9(4)
C14C
C15C
C19C
121.5(5)
C16C
C15C
C19C
119.6(4)
C15A
C16A
C17A
123.1(4)
C15B
C16B
C17B
122.8(4)
C15C
C16C
C17C
122.8(4)
C12A
C17A
C16A
116.8(4)
C12A
C17A
C20A
126.3(4)
C16A
C17A
C20A
116.9(4)
C12B
C17B
C16B
117.6(4)
C12B
C17B
C20B
125.4(4)
C16B
C17B
C20B
117.0(4)
C12C
C17C
C16C
117.2(4)
C12C
C17C
C20C
126.7(4)
C16C
C17C
C20C
116.1(4)Table 4
Experimental dihedral angles (deg).
Atom
Atom
Atom
Atom
Angle
Atom
Atom
Atom
Atom
Angle
S1A
N2A
C1A
O2A
20.7(5)
S1A
N2A
C1A
N1A
−158.4(2)
S1A
N2A
C3A
C2A
144.3(3)
S1A
C12A
C13A
C14A
174.9(3)
S1A
C12A
C13A
C18A
−4.1(5)
S1A
C12A
C17A
C16A
−175.1(3)
S1A
C12A
C17A
C20A
5.4(6)
S1B
N2B
C1B
O2B
17.4(5)
S1B
N2B
C1B
N1B
−162.1(3)
S1B
N2B
C3B
C2B
148.0(3)
S1B
C12B
C13B
C14B
−178.1(3)
S1B
C12B
C13B
C18B
2.7(6)
S1B
C12B
C17B
C16B
177.0(3)
S1B
C12B
C17B
C20B
−3.4(5)
S1C
N2C
C1C
O2C
23.1(6)
S1C
N2C
C1C
N1C
−156.5(3)
S1C
N2C
C3C
C2C
142.4(3)
S1C
C12C
C13C
C14C
175.0(3)
S1C
C12C
C13C
C18C
−5.3(6)
S1C
C12C
C17C
C16C
−173.8(3)
S1C
C12C
C17C
C20C
5.8(6)
O1A
C4A
N1A
C1A
167.1(4)
O1A
C4A
N1A
C2A
2.6(6)
O1A
C4A
C5A
C6A
0.1(6)
O1B
C4B
N1B
C1B
170.5(4)
O1B
C4B
N1B
C2B
8.5(5)
O1B
C4B
C5B
C6B
−13.6(6)
O1C
C4C
N1C
C1C
170.2(4)
O1C
C4C
N1C
C2C
4.7(6)
O1C
C4C
C5C
C6C
4.0(7)
O2A
C1A
N1A
C2A
−167.5(4)
O2A
C1A
N1A
C4A
26.8(6)
O2A
C1A
N2A
C3A
−175.7(4)
O2B
C1B
N1B
C2B
−167.0(4)
O2B
C1B
N1B
C4B
29.6(6)
O2B
C1B
N2B
C3B
−176.3(4)
O2C
C1C
N1C
C2C
−170.1(4)
O2C
C1C
N1C
C4C
23.3(6)
O2C
C1C
N2C
C3C
−171.9(4)
O3A
S1A
N2A
C1A
48.6(3)
O3A
S1A
N2A
C3A
−112.6(3)
O3A
S1A
C12A
C13A
171.4(3)
O3A
S1A
C12A
C17A
−10.7(4)
O3B
S1B
N2B
C1B
178.1(3)
O3B
S1B
N2B
C3B
13.6(4)
O3B
S1B
C12B
C13B
−142.5(3)
O3B
S1B
C12B
C17B
38.3(3)
O3C
S1C
N2C
C1C
42.0(3)
O3C
S1C
N2C
C3C
−120.7(3)
O3C
S1C
C12C
C13C
170.4(3)
O3C
S1C
C12C
C17C
−12.7(4)
O4A
S1A
N2A
C1A
174.9(3)
O4A
S1A
N2A
C3A
13.6(4)
O4A
S1A
C12A
C13A
38.0(3)
O4A
S1A
C12A
C17A
−144.1(3)
O4B
S1B
N2B
C1B
52.1(4)
O4B
S1B
N2B
C3B
−112.4(3)
O4B
S1B
C12B
C13B
−10.3(4)
O4B
S1B
C12B
C17B
170.5(3)
O4C
S1C
N2C
C1C
168.2(3)
O4C
S1C
N2C
C3C
5.4(4)
O4C
S1C
C12C
C13C
37.5(4)
O4C
S1C
C12C
C17C
−145.6(3)
N1A
C1A
N2A
C3A
5.2(4)
N1A
C2A
C3A
N2A
23.3(4)
N1A
C2A
C8A
C9A
54.5(5)
N1A
C2A
C8A
C10A
171.6(4)
N1A
C2A
C8A
C11A
−67.1(5)
N1A
C4A
C5A
C6A
176.7(4)
N1B
C1B
N2B
C3B
4.2(4)
N1B
C2B
C3B
N2B
23.2(4)
N1B
C2B
C8B
C9B
56.9(5)
N1B
C2B
C8B
C10B
176.3(4)
N1B
C2B
C8B
C11B
−63.7(5)
N1B
C4B
C5B
C6B
162.9(4)
N1C
C1C
N2C
C3C
8.5(4)
N1C
C2C
C3C
N2C
25.1(4)
N1C
C2C
C8C
C9C
52.0(5)
N1C
C2C
C8C
C10C
170.3(4)
N1C
C2C
C8C
C11C
−69.3(5)
N1C
C4C
C5C
C6C
−178.1(4)
N2A
S1A
C12A
C13A
−72.1(3)
N2A
S1A
C12A
C17A
105.8(3)
N2A
C1A
N1A
C2A
11.6(4)
N2A
C1A
N1A
C4A
−154.1(4)
N2A
C3A
C2A
C8A
−98.4(4)
N2B
S1B
C12B
C13B
106.4(3)
N2B
S1B
C12B
C17B
−72.7(3)
N2B
C1B
N1B
C2B
12.4(4)
N2B
C1B
N1B
C4B
−150.9(3)
N2B
C3B
C2B
C8B
−99.9(4)
N2C
S1C
C12C
C13C
−74.1(3)
N2C
S1C
C12C
C17C
102.9(3)
N2C
C1C
N1C
C2C
9.5(4)
N2C
C1C
N1C
C4C
−157.1(3)
N2C
C3C
C2C
C8C
−98.5(3)
C1A
N1A
C2A
C3A
−22.4(4)
C1A
N1A
C2A
C8A
99.1(4)
C1A
N1A
C4A
C5A
−9.6(6)
C1A
N2A
S1A
C12A
−69.5(3)
C1A
N2A
C3A
C2A
−18.8(4)
C1B
N1B
C2B
C3B
−22.8(4)
C1B
N1B
C2B
C8B
100.9(4)
C1B
N1B
C4B
C5B
−6.1(6)
C1B
N2B
S1B
C12B
−65.9(3)
C1B
N2B
C3B
C2B
−18.0(4)
C1C
N1C
C2C
C3C
−22.5(4)
C1C
N1C
C2C
C8C
100.3(4)
C1C
N1C
C4C
C5C
−7.8(6)
C1C
N2C
S1C
C12C
−75.1(3)
C1C
N2C
C3C
C2C
−21.9(4)
C2A
N1A
C4A
C5A
−174.2(3)
C2B
N1B
C4B
C5B
−168.1(3)
C2C
N1C
C4C
C5C
−173.4(4)
C3A
N2A
S1A
C12A
129.3(3)
C3A
C2A
N1A
C4A
144.2(3)
C3A
C2A
C8A
C9A
168.9(4)
C3A
C2A
C8A
C10A
−74.0(4)
C3A
C2A
C8A
C11A
47.3(5)
C3B
N2B
S1B
C12B
129.6(6)
C3B
C2B
N1B
C4B
141.7(3)
C3B
C2B
C8B
C19B
173.2(4)
C3B
C2B
C8B
C10B
−67.5(5)
C3B
C2B
C8B
C11B
52.5(5)
C3C
N2C
S1C
C12C
122.1(3)
C3C
C2C
N1C
C4C
145.0(3)
C3C
C2C
C8C
C9C
168.1(4)
C3C
C2C
C8C
C10C
−73.5(4)
C3C
C2C
C8C
C11C
46.9(5)
C4A
N1A
C2A
C8A
−94.3(4)
C4A
C5A
C6A
C7A
−173.9(4)
C4B
N1B
C2B
C8B
−94.7(4)
C4B
C5B
C6B
C7B
−173.8(5)
C4C
N1C
C2C
C8C
−92.3(4)
C4C
C5C
C6C
C7C
−173.4(5)
C12A
C13A
C14A
C15A
0.6(6)
C12A
C17A
C16A
C15A
−0.2(6)
C12B
C13B
C14B
C15B
1.3(6)
C12B
C17B
C16B
C15B
1.2(6)
C12C
C13C
C14C
C15C
−1.5(6)
C12C
C17C
C16C
C15C
−0.9(6)
C13A
C12A
C17A
C16A
2.7(5)
C13A
C12A
C17A
C20A
−176.8(4)
C13A
C14A
C15A
C16A
1.8(6)
C13A
C14A
C15A
C19A
−175.9(4)
C13B
C12B
C17B
C16B
−2.2(5)
C13B
C12B
C17B
C20B
177.4(4)
C13B
C14B
C15B
C16B
−2.3(6)
C13B
C14B
C15B
C19B
177.4(5)
C13C
C12C
C17C
C16C
3.0(6)
C13C
C12C
C17C
C20C
−177.4(4)
C13C
C14C
C15C
C16C
3.7(7)
C13C
C14C
C15C
C19C
−175.2(4)
C14A
C13A
C12A
C17A
−3.0(5)
C14A
C15A
C16A
C17A
−2.0(6)
C14B
C13B
C12B
C17B
1.0(5)
C14B
C15B
C16B
C17B
1.0(7)
C14C
C13C
C12C
C17C
1.9(6)
C14C
C15C
C16C
C17C
−2.4(7)
C15A
C14A
C13A
C18A
179.8(4)
C15A
C16A
C17A
C20A
179.4(4)
C15B
C14B
C13B
C18B
−179.4(4)
C15B
C16B
C17B
C20B
−178.5(4)
C15C
C14C
C13C
C18C
178.8(4)
C15C
C16C
C17C
C20C
179.5(4)
C17A
C12A
C13A
C18A
178.0(4)
C17A
C16A
C15A
C19A
175.6(4)
C17B
C12B
C13B
C18B
−178.2(4)
C17B
C16B
C15B
C19B
−178.7(4)
C17C
C12C
C13C
C18C
177.7(4)
C17C
C16C
C15C
C19C
176.5(4)Numbering system of the three molecules (3A; (a), 3B; (b), and 3C; (c)) of the X-ray structure of compound 3.
(a)
(b)
(c)


## 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).Table 1
Summary of crystal data, intensity data collection, and structure refinement for compound3 at 20.0°C.
(a)
Crystal data
Empirical formula
C20H30N2O4S
Formula weight
394.53
Crystal color, Habit
Colorless, plate
Crystal dimensions
0.25× 0.10 × 0.25 mm
Crystal system
Triclinic
Lattice type
Primitive
No. of reflections used for unit cell Determination (2θ range)
25 (59.2–59.9°)
Omega scan peak width at half-height
0.28°
Lattice parameters
a = 10.6216(5) Å
b = 16.532(1) Å
c = 8.9572(9) Å
α = 91.193(6)°
β = 93.849(6)°
γ = 88.097(4)°
V = 1568.2(2) Å3
Space group
P1 (#1)
Z value
3
D
calc
1.253 g/cm3
F
000
636.00
μ (CuKα)
15.98 cm−1
(b)
Intensity measurements
Diffractometer
Rigaku AFC7R
Radiation
CuKα (λ = 1.54178 Å)
Graphite monochromated
Attenuator
Ni foil (factor = 8.82)
Take-off angle
6.0°
Detector aperture
3.0 mm horizontal
3.0 mm vertical
Crystal to detector distance
235 mm
Voltage, current
35 kV, 150 mA
Temperature
20.0°C
Scan type
ω
-
2
θ
Scan rate
16.0°/min (inω) (up to 5 scans)
Scan Width
(1.78
+
0.30
tan
θ)°
2θ
max
120.1°
No. of reflections measured
Total: 4942
Unique: 4649 (R
int = 0.059)
(c)
Structure solution and refinement
Structure solution
Direct methods (SIR92)
Refinement
Full-matrix least-squares
P factor
0.0800
Anomalous dispersion
All nonhydrogen atoms
No. of observations(
I
>
3.00
σ
(
I
)
)
4409
No. of variables
729
Reflection/parameter ratio
6.05
Residuals:R; Rw
0.037; 0.056
ResidualsR1
0.037
No. of reflections to calcR1
4409
Goodness of fit indicator
1.26
Max shift/error in final cycle
0.09
Maximum peak in final diff. map
0.15 e−/Å3
Minimum peak in final diff. map
−0.20 e−/Å3Scheme 1
Synthesis of (4R)-(−)-1-(2,4,6-Trimethylbenzenesulfonyl)-3-n-butyryl-4-tert-butyl-2-imidazolidinone (3).The data were collected at a temperature of20
±
1°C using the ω
-
2
θ scan technique to a maximum 2
θ 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 (
1.78
+
0.30
tan
θ
)
° were made at a speed of 16.0°/min (in omega). The weak reflections (I
<
10.0
σ (I)) 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 (R
int
=
0.059); equivalent reflections were merged. The intensities of three representative reflections were measured after every 150 reflections. The linear absorption coefficient, μ, 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 (coefficient
=
6.35905
e
-
06).


## 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: ∑
ω
(
|
Fo
|
-
|
Fc
|
)
2, where w
=
1
/
σ
2
(
Fo
)
=
[
σ
c
2
(
Fo
)
+
(
p
2
/
4
)
F
o
2
]
-
1 and σ
c
2
(
Fo
)
=
e
.
s
.
d. based on counting, p
=
p
-factor) was based on 4409 observed reflections (I
>
3.00
σ (I)) and 729 variable parameters and converged (largest parameter shift was 0.09 times its esd) with unweighted and weighted agreement factors of
(1)
R
=
∑
|
|
Fo
|
-
|
Fc
|
|
∑
|
Fo
|
=
0.037
,
R
ω
=
∑
ω
(
|
Fo
|
-
|
Fc
|
)
2
∑
ω
F
o
2
=
0.056
.The standard deviation of an observation of unit weight (standard deviation of an observation of unit weight:∑
ω
(
|
Fo
|
-
|
Fc
|
)
2
/
(
No
-
Nv
), where: no
.
=
number of observations and nv
=
number of variables) was 1.26 and the weighting scheme was based on counting statistics and included a factor (P
=
0.080) to down-weight the intense reflections. Plots of ∑
ω
(
|
Fo
|
-
|
Fc
|
)
2 versus |
Fo
|, reflection order in data collection, sin θ
/
λ, 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 e
-
/
Å
3, respectively.Neutral atom scattering factors were taken from Cromer and Waber [24] and anomalous dispersion effects were included in Fcalc [25]; the values for Δ
f
′ and Δ
f
′
′ 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.Table 2
Experimental bond lengths (Å).
Atom
Atom
Distance
Atom
Atom
Distance
S1A
O3A
1.416(3)
S1A
O4A
1.428(3)
S1A
N2A
1.671(3)
S1A
C12A
1.777(4)
S1B
O3B
1.430(4)
S1B
O4B
1.421(4)
S1B
N2B
1.664(3)
S1B
C12B
1.773(4)
S1C
O3C
1.416(3)
S1C
O4C
1.425(3)
S1C
N2C
1.669(3)
S1C
C12C
1.768(4)
O1A
C4A
1.215(5)
O1B
C4B
1.219(5)
O1C
C4C
1.210(5)
O2A
C1A
1.200(4)
O2B
C1B
1.209(5)
O2C
C1C
1.203(5)
N1A
C1A
1.376(5)
N1A
C2A
1.485(5)
N1A
C4A
1.408(5)
N1B
C1B
1.380(5)
N1B
C2B
1.485(5)
N1B
C4B
1.401(5)
N1C
C1C
1.386(5)
N1C
C2C
1.476(5)
N1C
C4C
1.413(5)
N2A
C1A
1.395(5)
N2A
C3A
1.469(5)
N2B
C1B
1.386(5)
N2B
C3B
1.473(5)
N2C
C1C
1.386(5)
N2C
C3C
1.486(5)
C2A
C3A
1.523(5)
C2A
C8A
1.556(6)
C2B
C3B
1.531(5)
C2B
C8B
1.549(5)
C2C
C3C
1.520(5)
C2C
C8C
1.550(5)
C4A
C5A
1.507(6)
C4B
C5B
1.503(6)
C4C
C5C
1.486(6)
C5A
C6A
1.531(6)
C5B
C6B
1.507(7)
C5C
C6C
1.516(6)
C6A
C7A
1.490(8)
C6B
C7B
1.476(9)
C6C
C7C
1.492(9)
C8A
C9A
1.533(7)
C8A
C10A
1.533(6)
C8A
C11A
1.502(7)
C8B
C9B
1.515(7)
C8B
C10B
1.530(6)
C8B
C11B
1.508(7)
C8C
C9C
1.515(8)
C8C
C10C
1.523(6)
C8C
C11C
1.532(7)
C12A
C13A
1.401(5)
C12A
C17A
1.411(6)
C12B
C13B
1.412(6)
C12B
C17B
1.407(6)
C12C
C13C
1.410(6)
C12C
C17C
1.403(6)
C13A
C14A
1.383(6)
C13A
C18A
1.502(6)
C13B
C14B
1.408(7)
C13B
C18B
1.487(7)
C13C
C14C
1.404(6)
C13C
C18C
1.502(6)
C14A
C15A
1.377(6)
C14B
C15B
1.372(7)
C14C
C15C
1.355(7)
C15A
C16A
1.363(6)
C15A
C19A
1.500(6)
C15B
C16B
1.376(7)
C15B
C19B
1.507(8)
C15C
C16C
1.368(7)
C15C
C19C
1.503(7)
C16A
C17A
1.396(6)
C16B
C17B
1.392(7)
C16C
C17C
1.404(6)
C17A
C20A
1.500(6)
C17B
C20B
1.506(7)
C17C
C20C
1.506(6)Table 3
Experimental bond angles (deg).
Atom
Atom
Atom
Angle
Atom
Atom
Atom
Angle
O3A
S1A
O4A
118.5(2)
O3A
S1A
N2A
108.4(2)
O3A
S1A
C12A
110.8(2)
O4A
S1A
N2A
102.9(2)
O4A
S1A
C12A
110.6(2)
N2A
S1A
C12A
104.3(2)
O3B
S1B
O4B
117.6(2)
O3B
S1B
N2B
103.7(2)
O3B
S1B
C12B
110.8(2)
O4B
S1B
N2B
108.8(2)
O4B
S1B
C12B
110.5(2)
N2B
S1B
C12B
104.3(2)
O3C
S1C
O4C
118.2(2)
O3C
S1C
N2C
107.7(2)
O3C
S1C
C12C
110.1(2)
O4C
S1C
N2C
103.9(2)
O4C
S1C
C12C
111.2(2)
N2C
S1C
C12C
104.7(2)
C1A
N1A
C2A
111.9(3)
C1A
N1A
C4A
126.2(3)
C2A
N1A
C4A
120.4(3)
C1B
N1B
C2B
111.0(3)
C1A
N1B
C4B
126.4(3)
C2B
N1B
C4B
120.5(3)
C1C
N1C
C2C
111.7(3)
C1C
N1C
C4C
126.4(3)
C2C
N1C
C4C
120.5(3)
S1A
N2A
C1A
122.1(2)
S1A
N2A
C3A
124.5(2)
C1A
N2A
C3A
111.1(3)
S1B
N2B
C1B
122.6(3)
S1B
N2B
C3B
124.5(3)
C1B
N2B
C3B
111.3(3)
S1C
N2C
C1C
121.7(3)
S1C
N2C
C3C
125.4(3)
C1C
N2C
C3C
111.0(3)
O2A
C1A
N1A
128.9(3)
O2A
C1A
N2A
124.4(3)
N1A
C1A
N2A
106.7(3)
O2B
C1B
N1B
127.9(4)
O2B
C1B
N2B
124.7(4)
N1B
C1B
N2B
107.4(3)
O2C
C1C
N1C
128.0(4)
O2C
C1C
N2C
125.4(4)
N1C
C1C
N2C
106.6(3)
N1A
C2A
C3A
101.0(3)
N1A
C2A
C8A
113.5(3)
C3A
C2A
C8A
113.2(3)
N1B
C2B
C3B
101.6(3)
N1B
C2B
C8B
113.8(3)
C3B
C2B
C8B
114.6(3)
N1C
C2C
C3C
101.7(3)
N1C
C2C
C8C
114.6(3)
C3C
C2C
C8C
113.4(3)
N2A
C3A
C2A
103.3(3)
N2B
C3B
C2B
102.7(3)
N2C
C3C
C2C
102.2(3)
O1A
C4A
N1A
119.0(4)
O1A
C4A
C5A
122.7(4)
N1A
C4A
C5A
118.2(3)
O1B
C4B
N1B
119.1(4)
O1B
C4B
C5B
122.4(4)
N1B
C4B
C5B
118.4(3)
O1C
C4C
N1C
118.1(4)
O1C
C4C
C5C
123.5(4)
N1C
C4C
C5C
118.4(3)
C4A
C5A
C6A
111.4(4)
C4B
C5B
C6B
112.3(4)
C4C
C5C
C6C
112.5(4)
C5A
C6A
C7A
111.6(4)
C5B
C6B
C7B
112.3(5)
C5C
C6C
C7C
112.9(4)
C2A
C8A
C9A
110.3(4)
C2A
C8A
C10A
106.3(4)
C2A
C8A
C11A
113.9(3)
C9A
C8A
C10A
108.2(4)
C9A
C8A
C11A
108.0(5)
C10A
C8A
C11A
110.1(4)
C2B
C8B
C9B
110.9(3)
C2B
C8B
C10B
106.3(4)
C2B
C8B
C11B
112.0(3)
C9B
C8B
C10B
109.9(4)
C9B
C8B
C11B
107.9(4)
C10B
C8B
C11B
109.8(4)
C2C
C8C
C9C
110.8(4)
C2C
C8C
C10C
107.4(3)
C2C
C8C
C11C
111.8(3)
C9C
C8C
C10C
108.5(4)
C9C
C8C
C11C
108.6(5)
C10C
C8C
C11C
109.7(4)
S1A
C12A
C13A
118.1(3)
S1A
C12A
C17A
120.4(3)
C13A
C12A
C17A
121.4(4)
S1B
C12B
C13B
120.3(3)
S1B
C12B
C17B
118.3(3)
C13B
C128
C17B
121.3(4)
S1C
C12C
C13C
118.4(3)
S1C
C12C
C17C
120.7(3)
C13C
C12C
C17C
120.8(4)
C12A
C13A
C14A
117.5(4)
C12A
C13A
C18A
125.7(4)
C14A
C13A
C18A
116.8(4)
C12B
C13B
C14B
117.2(4)
C12B
C13B
C18B
127.2(4)
C14B
C13B
C18B
115.6(4)
C12C
C13C
C14C
117.8(4)
C12C
C13C
C18C
125.2(4)
C14C
C13C
C18C
117.0(4)
C13A
C14A
C15A
122.9(4)
C13B
C14B
C15B
122.4(4)
C13C
C14C
C15C
122.3(4)
C14A
C15A
C16A
118.2(4)
C14A
C15A
C19A
121.1(4)
C16A
C15A
C19A
120.6(4)
C14B
C15B
C16B
118.6(4)
C14B
C15B
C19B
120.2(5)
C16B
C15B
C19B
121.2(5)
C14C
C15C
C16C
118.9(4)
C14C
C15C
C19C
121.5(5)
C16C
C15C
C19C
119.6(4)
C15A
C16A
C17A
123.1(4)
C15B
C16B
C17B
122.8(4)
C15C
C16C
C17C
122.8(4)
C12A
C17A
C16A
116.8(4)
C12A
C17A
C20A
126.3(4)
C16A
C17A
C20A
116.9(4)
C12B
C17B
C16B
117.6(4)
C12B
C17B
C20B
125.4(4)
C16B
C17B
C20B
117.0(4)
C12C
C17C
C16C
117.2(4)
C12C
C17C
C20C
126.7(4)
C16C
C17C
C20C
116.1(4)Table 4
Experimental dihedral angles (deg).
Atom
Atom
Atom
Atom
Angle
Atom
Atom
Atom
Atom
Angle
S1A
N2A
C1A
O2A
20.7(5)
S1A
N2A
C1A
N1A
−158.4(2)
S1A
N2A
C3A
C2A
144.3(3)
S1A
C12A
C13A
C14A
174.9(3)
S1A
C12A
C13A
C18A
−4.1(5)
S1A
C12A
C17A
C16A
−175.1(3)
S1A
C12A
C17A
C20A
5.4(6)
S1B
N2B
C1B
O2B
17.4(5)
S1B
N2B
C1B
N1B
−162.1(3)
S1B
N2B
C3B
C2B
148.0(3)
S1B
C12B
C13B
C14B
−178.1(3)
S1B
C12B
C13B
C18B
2.7(6)
S1B
C12B
C17B
C16B
177.0(3)
S1B
C12B
C17B
C20B
−3.4(5)
S1C
N2C
C1C
O2C
23.1(6)
S1C
N2C
C1C
N1C
−156.5(3)
S1C
N2C
C3C
C2C
142.4(3)
S1C
C12C
C13C
C14C
175.0(3)
S1C
C12C
C13C
C18C
−5.3(6)
S1C
C12C
C17C
C16C
−173.8(3)
S1C
C12C
C17C
C20C
5.8(6)
O1A
C4A
N1A
C1A
167.1(4)
O1A
C4A
N1A
C2A
2.6(6)
O1A
C4A
C5A
C6A
0.1(6)
O1B
C4B
N1B
C1B
170.5(4)
O1B
C4B
N1B
C2B
8.5(5)
O1B
C4B
C5B
C6B
−13.6(6)
O1C
C4C
N1C
C1C
170.2(4)
O1C
C4C
N1C
C2C
4.7(6)
O1C
C4C
C5C
C6C
4.0(7)
O2A
C1A
N1A
C2A
−167.5(4)
O2A
C1A
N1A
C4A
26.8(6)
O2A
C1A
N2A
C3A
−175.7(4)
O2B
C1B
N1B
C2B
−167.0(4)
O2B
C1B
N1B
C4B
29.6(6)
O2B
C1B
N2B
C3B
−176.3(4)
O2C
C1C
N1C
C2C
−170.1(4)
O2C
C1C
N1C
C4C
23.3(6)
O2C
C1C
N2C
C3C
−171.9(4)
O3A
S1A
N2A
C1A
48.6(3)
O3A
S1A
N2A
C3A
−112.6(3)
O3A
S1A
C12A
C13A
171.4(3)
O3A
S1A
C12A
C17A
−10.7(4)
O3B
S1B
N2B
C1B
178.1(3)
O3B
S1B
N2B
C3B
13.6(4)
O3B
S1B
C12B
C13B
−142.5(3)
O3B
S1B
C12B
C17B
38.3(3)
O3C
S1C
N2C
C1C
42.0(3)
O3C
S1C
N2C
C3C
−120.7(3)
O3C
S1C
C12C
C13C
170.4(3)
O3C
S1C
C12C
C17C
−12.7(4)
O4A
S1A
N2A
C1A
174.9(3)
O4A
S1A
N2A
C3A
13.6(4)
O4A
S1A
C12A
C13A
38.0(3)
O4A
S1A
C12A
C17A
−144.1(3)
O4B
S1B
N2B
C1B
52.1(4)
O4B
S1B
N2B
C3B
−112.4(3)
O4B
S1B
C12B
C13B
−10.3(4)
O4B
S1B
C12B
C17B
170.5(3)
O4C
S1C
N2C
C1C
168.2(3)
O4C
S1C
N2C
C3C
5.4(4)
O4C
S1C
C12C
C13C
37.5(4)
O4C
S1C
C12C
C17C
−145.6(3)
N1A
C1A
N2A
C3A
5.2(4)
N1A
C2A
C3A
N2A
23.3(4)
N1A
C2A
C8A
C9A
54.5(5)
N1A
C2A
C8A
C10A
171.6(4)
N1A
C2A
C8A
C11A
−67.1(5)
N1A
C4A
C5A
C6A
176.7(4)
N1B
C1B
N2B
C3B
4.2(4)
N1B
C2B
C3B
N2B
23.2(4)
N1B
C2B
C8B
C9B
56.9(5)
N1B
C2B
C8B
C10B
176.3(4)
N1B
C2B
C8B
C11B
−63.7(5)
N1B
C4B
C5B
C6B
162.9(4)
N1C
C1C
N2C
C3C
8.5(4)
N1C
C2C
C3C
N2C
25.1(4)
N1C
C2C
C8C
C9C
52.0(5)
N1C
C2C
C8C
C10C
170.3(4)
N1C
C2C
C8C
C11C
−69.3(5)
N1C
C4C
C5C
C6C
−178.1(4)
N2A
S1A
C12A
C13A
−72.1(3)
N2A
S1A
C12A
C17A
105.8(3)
N2A
C1A
N1A
C2A
11.6(4)
N2A
C1A
N1A
C4A
−154.1(4)
N2A
C3A
C2A
C8A
−98.4(4)
N2B
S1B
C12B
C13B
106.4(3)
N2B
S1B
C12B
C17B
−72.7(3)
N2B
C1B
N1B
C2B
12.4(4)
N2B
C1B
N1B
C4B
−150.9(3)
N2B
C3B
C2B
C8B
−99.9(4)
N2C
S1C
C12C
C13C
−74.1(3)
N2C
S1C
C12C
C17C
102.9(3)
N2C
C1C
N1C
C2C
9.5(4)
N2C
C1C
N1C
C4C
−157.1(3)
N2C
C3C
C2C
C8C
−98.5(3)
C1A
N1A
C2A
C3A
−22.4(4)
C1A
N1A
C2A
C8A
99.1(4)
C1A
N1A
C4A
C5A
−9.6(6)
C1A
N2A
S1A
C12A
−69.5(3)
C1A
N2A
C3A
C2A
−18.8(4)
C1B
N1B
C2B
C3B
−22.8(4)
C1B
N1B
C2B
C8B
100.9(4)
C1B
N1B
C4B
C5B
−6.1(6)
C1B
N2B
S1B
C12B
−65.9(3)
C1B
N2B
C3B
C2B
−18.0(4)
C1C
N1C
C2C
C3C
−22.5(4)
C1C
N1C
C2C
C8C
100.3(4)
C1C
N1C
C4C
C5C
−7.8(6)
C1C
N2C
S1C
C12C
−75.1(3)
C1C
N2C
C3C
C2C
−21.9(4)
C2A
N1A
C4A
C5A
−174.2(3)
C2B
N1B
C4B
C5B
−168.1(3)
C2C
N1C
C4C
C5C
−173.4(4)
C3A
N2A
S1A
C12A
129.3(3)
C3A
C2A
N1A
C4A
144.2(3)
C3A
C2A
C8A
C9A
168.9(4)
C3A
C2A
C8A
C10A
−74.0(4)
C3A
C2A
C8A
C11A
47.3(5)
C3B
N2B
S1B
C12B
129.6(6)
C3B
C2B
N1B
C4B
141.7(3)
C3B
C2B
C8B
C19B
173.2(4)
C3B
C2B
C8B
C10B
−67.5(5)
C3B
C2B
C8B
C11B
52.5(5)
C3C
N2C
S1C
C12C
122.1(3)
C3C
C2C
N1C
C4C
145.0(3)
C3C
C2C
C8C
C9C
168.1(4)
C3C
C2C
C8C
C10C
−73.5(4)
C3C
C2C
C8C
C11C
46.9(5)
C4A
N1A
C2A
C8A
−94.3(4)
C4A
C5A
C6A
C7A
−173.9(4)
C4B
N1B
C2B
C8B
−94.7(4)
C4B
C5B
C6B
C7B
−173.8(5)
C4C
N1C
C2C
C8C
−92.3(4)
C4C
C5C
C6C
C7C
−173.4(5)
C12A
C13A
C14A
C15A
0.6(6)
C12A
C17A
C16A
C15A
−0.2(6)
C12B
C13B
C14B
C15B
1.3(6)
C12B
C17B
C16B
C15B
1.2(6)
C12C
C13C
C14C
C15C
−1.5(6)
C12C
C17C
C16C
C15C
−0.9(6)
C13A
C12A
C17A
C16A
2.7(5)
C13A
C12A
C17A
C20A
−176.8(4)
C13A
C14A
C15A
C16A
1.8(6)
C13A
C14A
C15A
C19A
−175.9(4)
C13B
C12B
C17B
C16B
−2.2(5)
C13B
C12B
C17B
C20B
177.4(4)
C13B
C14B
C15B
C16B
−2.3(6)
C13B
C14B
C15B
C19B
177.4(5)
C13C
C12C
C17C
C16C
3.0(6)
C13C
C12C
C17C
C20C
−177.4(4)
C13C
C14C
C15C
C16C
3.7(7)
C13C
C14C
C15C
C19C
−175.2(4)
C14A
C13A
C12A
C17A
−3.0(5)
C14A
C15A
C16A
C17A
−2.0(6)
C14B
C13B
C12B
C17B
1.0(5)
C14B
C15B
C16B
C17B
1.0(7)
C14C
C13C
C12C
C17C
1.9(6)
C14C
C15C
C16C
C17C
−2.4(7)
C15A
C14A
C13A
C18A
179.8(4)
C15A
C16A
C17A
C20A
179.4(4)
C15B
C14B
C13B
C18B
−179.4(4)
C15B
C16B
C17B
C20B
−178.5(4)
C15C
C14C
C13C
C18C
178.8(4)
C15C
C16C
C17C
C20C
179.5(4)
C17A
C12A
C13A
C18A
178.0(4)
C17A
C16A
C15A
C19A
175.6(4)
C17B
C12B
C13B
C18B
−178.2(4)
C17B
C16B
C15B
C19B
−178.7(4)
C17C
C12C
C13C
C18C
177.7(4)
C17C
C16C
C15C
C19C
176.5(4)Numbering system of the three molecules (3A; (a), 3B; (b), and 3C; (c)) of the X-ray structure of compound 3.
(a)
(b)
(c)


## 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 molecule3 (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).


## 2.3.1. Conformational Search

Conformational analyses of isolated molecule3 (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 compound3, 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 of3 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 P
1 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, n-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 s
p
3 angle of 109.5°) [36]. Atoms system ∠N2–C3–C2 of 3A, 3B, and 3C are deviated from ideal s
p
3 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.Figure 2
The superposition of the three molecules (molecule3A: colors blue, molecule 3B: colors yellow, and molecule 3C: colors red) of X-ray structure of compound 3.Crystal packing of compound3 (a). (b) Shows intermolecular CH-O, CH-π (green lines), and π-π interactions (orange line). Hydrogen atoms are omitted for clarity except hydrogen included in CH-O interaction.
(a)
(b)To conclude, it is found that the solid state conformations of the three molecules of3 (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 of3 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.Figure 4
Results of conformational search showing most stable energy minimum:conformer-A (a), conformer-B (b), and the least stable conformers, including conformer-C (c), conformer-D (d), conformer-E (e), and conformer-F (f).Most stable energy minimum (conformer-A) as energy optimized with MM+ force field (a) and both AM1 (b) and PM3 (c) semiempirical molecular orbital methods showing some geometrical parameters such as bond length, bond angle, and dihedral angle.
(a)
(b)
(c)


#### 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 compound3 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 3was 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).Table 5
Heat of formations, relative energies, dipole moments, and selected geometric parameters for the significant conformations of3 computed using semiempirical AM1 MO level of theory. Comparative analysis with crystal structure 3
a.
Propertya
Conformer
Conformer
Conformer
Conformer
Conformer
Conformer
X-ray
A
b,c
B
C
D
E
F
3A
3B
3C
∠C1–N1–C4–C5
−23.8
−24.6
−28.0
−24.7
156.4
137.9
−9.6
−6.1
−7.8
(−9.9, −40.8 )
∠C1–N2–S1–C12
−61.7
61.7
−109.1
136.3
−45.7
−107.7
−69.5
−65.9
−75.1
(−46.2, −68.1)
∠N2–S1–C12–C13
−81.5
−98.3
−97.7
−81.2
−80.3
83.7
−72.1
−72.7
−73.5
(−71.8, −75.2)
∠C3–C2–C8–C10
−65.9
−62.7
−63.9
−62.5
−66.8
−59.9
−74.0
−67.5
−73.5
(−64.9, −55.1)
∠C1–N1–C2
110.0
109.9
110.1
109.9
109.0
110.7
111.9
111.0
111.0
(110.3, 109.5)
∠C1–N2–C3
108.8
108.7
108.8
108.8
108.7
108.8
111.1
111.3
111.0
(112.4, 108.6)
N1−C4
1.410
1.410
1.41
1.41
1.41
1.41
1.408
1.401
1.413
(1.39, 1.45)
N2−S1
1.67
1.67
1.67
1.67
1.67
1.66
1.777
1.664
1.669
(1.68, 1.79)
S1−C12
1.68
1.68
1.69
1.69
1.67
1.69
1.671
1.773
1.768
(1.80, 1.79)
Hf (kcal/mol)
−135.596
−135.069
−134.115
−132.739
128.334
127.122
—
—
—
Er (kcal/mol)
0.000
0.527
1.481
2.857
7.262
8.474
—
—
—
Dipole (Debye)
3.57
4.45
4.90
6.35
5.06
9.01
—
—
—
aAll values correspond to fully optimized geometries.
bRelative energies for the three similar conformations resulted from the separate conformational analysis of 3A, 3B, and 3C around the N1–C4 and N2–S1 bonds: 0.000, 0.110, and 0.05 kcal/mol, respectively.
cValues in bold, plain, and italic text corresponding to MM+, AM1, and PM3 geometry optimization, respectively.The arrangement around the N2–S1 and N1–C4 bonds mainly determines the geometry of theN-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 conformationsA-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 stableconformer-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 of3 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.Figure 6
The superposition of the theoretical model (conformer-A(colors green))and the three molecules (molecule 3A, colors blue, molecule 3B: colors yellow, and molecule 3C: colors red) of X-ray structure of compound 3.


## 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 of3 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 P
1 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, n-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 s
p
3 angle of 109.5°) [36]. Atoms system ∠N2–C3–C2 of 3A, 3B, and 3C are deviated from ideal s
p
3 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.Figure 2
The superposition of the three molecules (molecule3A: colors blue, molecule 3B: colors yellow, and molecule 3C: colors red) of X-ray structure of compound 3.Crystal packing of compound3 (a). (b) Shows intermolecular CH-O, CH-π (green lines), and π-π interactions (orange line). Hydrogen atoms are omitted for clarity except hydrogen included in CH-O interaction.
(a)
(b)To conclude, it is found that the solid state conformations of the three molecules of3 (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 of3 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.Figure 4
Results of conformational search showing most stable energy minimum:conformer-A (a), conformer-B (b), and the least stable conformers, including conformer-C (c), conformer-D (d), conformer-E (e), and conformer-F (f).Most stable energy minimum (conformer-A) as energy optimized with MM+ force field (a) and both AM1 (b) and PM3 (c) semiempirical molecular orbital methods showing some geometrical parameters such as bond length, bond angle, and dihedral angle.
(a)
(b)
(c)


### 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 compound3 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 3was 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).Table 5
Heat of formations, relative energies, dipole moments, and selected geometric parameters for the significant conformations of3 computed using semiempirical AM1 MO level of theory. Comparative analysis with crystal structure 3
a.
Propertya
Conformer
Conformer
Conformer
Conformer
Conformer
Conformer
X-ray
A
b,c
B
C
D
E
F
3A
3B
3C
∠C1–N1–C4–C5
−23.8
−24.6
−28.0
−24.7
156.4
137.9
−9.6
−6.1
−7.8
(−9.9, −40.8 )
∠C1–N2–S1–C12
−61.7
61.7
−109.1
136.3
−45.7
−107.7
−69.5
−65.9
−75.1
(−46.2, −68.1)
∠N2–S1–C12–C13
−81.5
−98.3
−97.7
−81.2
−80.3
83.7
−72.1
−72.7
−73.5
(−71.8, −75.2)
∠C3–C2–C8–C10
−65.9
−62.7
−63.9
−62.5
−66.8
−59.9
−74.0
−67.5
−73.5
(−64.9, −55.1)
∠C1–N1–C2
110.0
109.9
110.1
109.9
109.0
110.7
111.9
111.0
111.0
(110.3, 109.5)
∠C1–N2–C3
108.8
108.7
108.8
108.8
108.7
108.8
111.1
111.3
111.0
(112.4, 108.6)
N1−C4
1.410
1.410
1.41
1.41
1.41
1.41
1.408
1.401
1.413
(1.39, 1.45)
N2−S1
1.67
1.67
1.67
1.67
1.67
1.66
1.777
1.664
1.669
(1.68, 1.79)
S1−C12
1.68
1.68
1.69
1.69
1.67
1.69
1.671
1.773
1.768
(1.80, 1.79)
Hf (kcal/mol)
−135.596
−135.069
−134.115
−132.739
128.334
127.122
—
—
—
Er (kcal/mol)
0.000
0.527
1.481
2.857
7.262
8.474
—
—
—
Dipole (Debye)
3.57
4.45
4.90
6.35
5.06
9.01
—
—
—
aAll values correspond to fully optimized geometries.
bRelative energies for the three similar conformations resulted from the separate conformational analysis of 3A, 3B, and 3C around the N1–C4 and N2–S1 bonds: 0.000, 0.110, and 0.05 kcal/mol, respectively.
cValues in bold, plain, and italic text corresponding to MM+, AM1, and PM3 geometry optimization, respectively.The arrangement around the N2–S1 and N1–C4 bonds mainly determines the geometry of theN-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 conformationsA-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 stableconformer-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 of3 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.Figure 6
The superposition of the theoretical model (conformer-A(colors green))and the three molecules (molecule 3A, colors blue, molecule 3B: colors yellow, and molecule 3C: colors red) of X-ray structure of compound 3.


## 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 compound3 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 3was 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).Table 5
Heat of formations, relative energies, dipole moments, and selected geometric parameters for the significant conformations of3 computed using semiempirical AM1 MO level of theory. Comparative analysis with crystal structure 3
a.
Propertya
Conformer
Conformer
Conformer
Conformer
Conformer
Conformer
X-ray
A
b,c
B
C
D
E
F
3A
3B
3C
∠C1–N1–C4–C5
−23.8
−24.6
−28.0
−24.7
156.4
137.9
−9.6
−6.1
−7.8
(−9.9, −40.8 )
∠C1–N2–S1–C12
−61.7
61.7
−109.1
136.3
−45.7
−107.7
−69.5
−65.9
−75.1
(−46.2, −68.1)
∠N2–S1–C12–C13
−81.5
−98.3
−97.7
−81.2
−80.3
83.7
−72.1
−72.7
−73.5
(−71.8, −75.2)
∠C3–C2–C8–C10
−65.9
−62.7
−63.9
−62.5
−66.8
−59.9
−74.0
−67.5
−73.5
(−64.9, −55.1)
∠C1–N1–C2
110.0
109.9
110.1
109.9
109.0
110.7
111.9
111.0
111.0
(110.3, 109.5)
∠C1–N2–C3
108.8
108.7
108.8
108.8
108.7
108.8
111.1
111.3
111.0
(112.4, 108.6)
N1−C4
1.410
1.410
1.41
1.41
1.41
1.41
1.408
1.401
1.413
(1.39, 1.45)
N2−S1
1.67
1.67
1.67
1.67
1.67
1.66
1.777
1.664
1.669
(1.68, 1.79)
S1−C12
1.68
1.68
1.69
1.69
1.67
1.69
1.671
1.773
1.768
(1.80, 1.79)
Hf (kcal/mol)
−135.596
−135.069
−134.115
−132.739
128.334
127.122
—
—
—
Er (kcal/mol)
0.000
0.527
1.481
2.857
7.262
8.474
—
—
—
Dipole (Debye)
3.57
4.45
4.90
6.35
5.06
9.01
—
—
—
aAll values correspond to fully optimized geometries.
bRelative energies for the three similar conformations resulted from the separate conformational analysis of 3A, 3B, and 3C around the N1–C4 and N2–S1 bonds: 0.000, 0.110, and 0.05 kcal/mol, respectively.
cValues in bold, plain, and italic text corresponding to MM+, AM1, and PM3 geometry optimization, respectively.The arrangement around the N2–S1 and N1–C4 bonds mainly determines the geometry of theN-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 conformationsA-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 stableconformer-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 of3 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.Figure 6
The superposition of the theoretical model (conformer-A(colors green))and the three molecules (molecule 3A, colors blue, molecule 3B: colors yellow, and molecule 3C: colors red) of X-ray structure of compound 3.


## 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 3was 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:deposit@ccdc.cam.ac.uk).



---

*Source: 173902-2014-01-05.xml*