Synthesis and crystal structure of 1-[2-(3-ethyl-2,2-dimethylcyclobutyl) acetyl]-3-phenylthiourea

Article abstract of DOI:10.4314/bcse.v27i1.13

The title compound 1-[2-(3-ethyl-2,2-dimethylcyclobutyl)acetyl]-3- phenylthiourea has been synthesized and its crystal structure was studied. The crystal belongs to triclinic system, space group P-1, a = 10.200(2) A, b = 12.395(3) A, c = 15.679(3) A, α = 92.99(2)o, β = 106.00(3)o, γ = 111.95(3)o, V = 1740.4(6) A3, Z = 2, μ = 0.187 mm-1, Dc = 1.162 g/cm3, F(000) = 656, R = 0.0784, wR2 = 0.1505, formula unit C₁₇H₂₄N₂OS. The title compound has a fragment of 2,2-dimethylcyclobutane and its conformation represents semi-chair. The intermolecular and intramolecular hydrogen bonds are revealed.

Full text of DOI:10.4314/bcse.v27i1.13

Bull. Chem. Soc. Ethiop. 2013, 27(1), 125-129.
Printed in Ethiopia
ISSN 1011-3924
 2013 Chemical Society of Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v27i1.13
SHORT COMMUNICATION
SYNTHESIS AND CRYSTAL STRUCTURE OF 1-[2-(3-ETHYL-2,2-
DIMETHYLCYCLOBUTYL)ACETYL]-3-PHENYLTHIOUREA
Yan-bai Yin1, Zhi-Qiang Yu2, Ya-Li Zhang1, Jian-Hua Hu1 and Zhan-qian Song3*
1Jining Institute of Supervision & Inspection on Product Quality, Jining, 272000, China
2Guohong Chemical Co., Ltd., Yankuang Group, Jining, 273512, China
3Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing,
210042, China
(Received December 02, 2011; revised May 9, 2012)
ABSTRACT. The title compound 1-[2-(3-ethyl-2,2-dimethylcyclobutyl)acetyl]-3-phenylthiourea has been
synthesized and its crystal structure was studied. The crystal belongs to triclinic system, space group P-1, a =
10.200(2) Ǻ, b = 12.395(3) Å, c = 15.679(3) Å, α = 92.99(2)o, β = 106.00(3)o, γ = 111.95(3)o, V = 1740.4(6) Å3,
Z = 2, µ = 0.187 mm−1, Dc = 1.162 g/cm3, F(000) = 656, R = 0.0784, wR2 = 0.1505, formula unit C17H24N2OS.
The title compound has a fragment of 2,2-dimethylcyclobutane and its conformation represents semi-chair. The
intermolecular and intramolecular hydrogen bonds are revealed.
KEY WORDS: Synthesis, Single crystal X-ray diffraction, Crystal structure, 2,2-Dimethylcyclobutane
INTRODUCTION
Many thiourea compounds exhibit strong structure stabilization and interesting biological
activities. So in recent years the synthesis and their biological activities have been studied.
Many cyclobutyl analogues also have favorable bioactivities [1-3]. So the thiourea compounds
containing cyclobutane ring may have interesting biological activities. In this paper we reported
the synthesis and crystal structure of 1-[2-(3-ethyl-2,2-dimethylcyclobutyl)acetyl]-3-phenyl-
thiourea. In the present contribution the synthesis of the title compound has been performed
according to the scheme shown in Figure 1.
OH
SOCl2
Cl
KSCN
O
O
O
H
N
H
NCS
N
O
S
Figure 1. The synthesis scheme of the title compound
In order to determine the structure and configuration of the title compound X-ray diffraction
study has been carried out.
__________
*Corresponding author. E-mail: fengzhongyuzhe@163.com

126
Zhan-qian Song et al.
EXPERIMENTAL
Synthesis. 2,2-Dimethyl-3-ethylcyclobutaneacetic acid was prepared in our laboratory according
to literature [4]. The title compound was synthesized according to following method: 2,2-
dimethyl-3-ethylcyclo-butaneacetic acid (5.0 g, 0.029 mol) was dissolved in the mixture of
dichloromethane (40 mL) and SOCl2 (4.5 mL, 0.062 mol), and the mixture was stirred and
refluxed for 4 h. Then the excessive solution was removed by decompression distillation. The
residue was added dropwise to the mixture of KSCN (3.0 g, 0.030 mol) and acetonitrile (30
mL). The resulting mixture was stirred for 4 h at room temperature. Aniline (2.70 g, 0.029 mol)
was added into the mixture. The reaction mixture was refluxed for 7 h. Then the excessive
solution was removed by decompression distillation and the residue was poured into water (70
mL). Finally pumping filtration left the crude product as yellow powder. The solid was purified
o
by recrystallization with ethanol in 83.9% yield. Melting point: 99.0-100.0 C. IR (KBr) ν: cm-1
1
3191 (N-H), 3036 (C=H), 1695 (C=O), 1252 (C-N), 1164 (C=S). H NMR (δ, ppm, CDCl3):
12.38 (s, 1H, NH), 9.05 (s, 1H, NH), 7.65 (d, 2H, C6H5), 7.38 (m, 2H, C6H5), 7.25 (m, 1H,
C6H5), 2.51, 2.30 (m, 2H, CH2), 2.40,2.18 (m, 2H, CH2), 1.77 (m, 2H, CH2), 1.35 (m, 1H, CH),
1.20 (m, 1H, CH), 1.08-0.89 (m, 6H, CH3), 0.80 (q, 3H, CH3).
X-ray diffraction study. Experimental X-ray diffraction data were obtained on a Enraf-Nonius
CAD4 diffractometer (graphite-monochromated MoKα radiation, λ = 0.71073 Å) by ω/2θ
scanning. Data were collected in the θ range of 1.4–25.3° (range of indices: 0≤h≤12, –14≤k ≤13,
-18≤l≤18). The structure was solved and refined with SHELX-97 software. All H atoms were
placed geometrically, with the C–H distances in the range 0.93-0.98 Å and N–H distances 0.86
Å, and included in the refinement in riding motion approximation with Uiso(H) = 1.2 or
1.5Ueq(H) of the carrier atom. Selected crystallographic data and experiment parameters are
listed in Table 1. Full crystallographic data for the compound of this study have been deposited
with Cambridge Crystallographic Data Centre (www.ccdc.cam.ac.uk), CCDC deposition
number 729335.
Table 1. Selected crystallographic data and experiment parameters.
Gross formula
C17H24N2OS
Molecular weight
Temperature, K
Symmetry and space group
a, b, c, Å
304.44
293(2)
Triclinic, P-1
10.200(2), 12.395(3), 15.679(3)
α, β, γ, deg
92.99(2), 106.00(3), 111.95(3)
1740.4(6)
V, Å3
Z
2
Ρcalc, g/cm3
1.162
Crystal dimensions, mm
Absorption coefficient, mm-1
Measured/observed reflections
Rint
0.30 × 0.20 × 0.10 mm
0.187
6718/6332
0.0310
Refined parameters
R factor [I > 2σ (I )]
R factor (all data)
Goof value
349
R1 = 0.0784, wR2 = 0.1505
R1 = 0.1498, wR2 = 0.1774
1.011
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RESULTS AND DISCUSSION
The IR and 1H NMR for the product are in good agreement with the title compound. In order to
determine the structure and configuration of title compound X-ray diffraction study has been
carried out. Figure 2 illustrates the structure of the title compound. As a whole, the molecule is
substantially non-planar. The 2,2-dimethylcyclobutane fragment is not flat and the conformation
represents semi-chair. The cyclobutane ring is flexed as though folded from the
dimethylsubstituted C atom to the unsubstituted C atom, with a dihedral angle of 17.5o. This is a
little different from other compounds containing cyclobutane rings. In ( )-2-[(1S,3S)-3-acetyl-
2,2-dimethylcyclobutyl]-N-(p-tolyl)acetamide the dihedral angle is 23.7o [5]; in ( )-cis-pinonic
acid [6] and (1S, 3S)-(+)-cis-3-acetyl-2,2-dimethylcyclobutaneacetic acid [7] the dihedral angle
is 29.8o; in (+)-trans-pinonic acid [8] the angle is 19.1o; in methyl ( )-2-((1R,3R)-3-{2-[(3S)-1-
ethyl-3-hydroxy-2-oxo-2,3-dihydro-1H-3-indolyl]acetyl}-2,2-dimethylcyclobutyl) acetate [9] the
angle is 18.6o; in (-)-cis-3-acetyl-2,2-dimethylcyclobutanecarboxylic acid [10] the angle is 25.5o.
The selected bond lengths and bond angles are listed in Table 2 and 3.
Figure 2. View of the structure of the title compound. Ellipsoids are drawn at the 50%
probability level.
Table 2. Selected bond lengths (Å).
Bond
S1-C11
N1-C10
N1-H1A
N2-C12
C1-C2
C1-H1C
C2-C3
C2-H2C
C3-C4
Length
1.642(7)
1.377(8)
0.8600
1.430(8)
1.473(8)
0.9600
1.450(7)
0.9700
1.560(10)
1.634(10)
0.9700
Bond
Length
1.222(8)
1.399(8)
1.312(8)
0.8600
0.9600
0.9600
0.9700
1.461(10)
0.9800
Bond
C7-H7C
C8-H8B
C9-C10
C9-H9B
C12-C13
C13-C18
C14-H14A
C6-C7
Length
0.9600
0.9600
1.512(9)
0.9700
1.373(9)
Bond
Length
0.9600
0.9600
0.9700
O1-C10
N1-C11
N2-C11
N2-H2A
C1-H1B
C1-H1D
C2-H2B
C3-C6
C8-H8A
C8-H8C
C9-H9A
C12-C17 1.370(10)
C13-C14 1.399(10)
1.551(10) C14-C15 1.359(11)
0.9300
1.466(7)
0.8600
0.9600
1.502(10)
C15-C16 1.350(11)
C16-C17 1.392(10)
C6-C8
C7-H7B
C5-H5A
C3-H3A
C4-H4A
C5-C6
N4-H4C
C7-H7A
C5-C9
1.533(11)
0.9600
0.9800
C4-C5
C4-H4B
0.9700
1.469(10)
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Zhan-qian Song et al.
Table 3. Selected bond angles and torsion angles.
Angles
(O)
129.5(6)
115.2
115.9
109.5
109.5
109.5
5.6(16)
172.1(6)
-22
Angles
(O)
115.2
128.1(6)
115.9
109.5
109.5
Angles
C3-C2-C1
(O)
116.6(8)
108.1
108.1
108.1
C10-N1-C11
C11-N1-H1A
C11-N2-H2A
C2-C1-H1B
H1B-C1-H1C
H1B-C1-H1D
C1-C2-C3-C5
C6-C4-C9-C10
H4A-C4-C5-H5B
H4A-C4-C6-C8,
C2-C3-C6-C4
C5-C3-C6-C4
C10-N1-H1A
C11-N2-C12
C12-N2-H2A
C2-C1-H1C
C1-C2-H2B
C3-C2-H2B
C3-C2-H2C
C1-C2-H2C
H2B-C2-H2C
C5-C4-C9-C10
C6-C3-C5-C4
H4A-C4-C6-C7
C6-C3-C5-C4
C2-C3-C6-C8
C5-C3-C6-C8
C2-C1-H1D
108.1
107.3
H1C-C1-H1D
C1-C2-C3-C6
C6-C4-C5-C3
H4A-C4-C6-C3
C2-C3-C5-C4
C2-C3-C6-C7
C5-C3-C6-C7
109.5
-174.4(10)
-11.8(7)
-95
-167.8(10)
-77.4(13)
102.6(8)
-72.3(10)
12.2(7)
150
12.2(7)
49.6(16)
-130.4(8)
25
168.3(12)
-11.7(6)
The C12 atom containing in the benzene ring, S1, N1, N2 and C11 are in the same plane.
The dihedral angel between the plane and the benzene ring is 49.9(2)o. There are two
intramolecular hydrogen bonds and two intermolecular hydrogen bonds in the title compound
which contributes to the stabilization of the crystal structure. The hydrogen bonds are shown in
the Figure 3 and Table 4.
Figure 3. The hydrogen bonds of the title compound.
N4, H4B and O2 form a intramolecular hydrogen bond and on account of the hydrogen
bond N4, C28, N3, C27 and O2 form a 6-membered ring. The C-N bond length on the sides of
C28=S2 bond are varied greatly. The bond length of C28-N4 (1.326(7) Å) is shorter than that of
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C28-N3 (1.383(7) Å). The bond length of C28=S2 is 1.66 (6) Å longer than the normal bond
length of C=S H(1A) due to the intermolecular hydrogen bond of N(1)—H(1A)…S(2).
Table 4. Hydrogen-bond geometry (Å, o) of the title compound.
D—H…A
D—H
0.86
0.86
0.86
0.86
0.97
0.93
H…A
2.62
1.96
2.64
1.92
2.78
D…A
D—H…A
165
N(1)—H(1A)…S(2)a,b
N(2)—H(2A)…O(1)c
N(3)—H(3A)…S(1)a,b
N(4)—H(4B)…O(2)c
C(26)—H(26B)…S(1)a,b
C(34)—H(34A)…S(2)c
3.460(6)
2.666(5)
3.466(5)
2.637(7)
3.701(8)
3.267(6)
138
163
140
159
2.81
111
c
a
b
Note. Elements of symmetry transformation: 1-x, -y, 1-z
hydrogen bond.
intermolecular hydrogen bond; intramolecular
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Bull. Chem. Soc. Ethiop. 2013, 27(1)