Synthesis, structural characterization and quantum chemical calculations on 1-(isomeric methylbenzoyl)-3-(4-trifluoromethylphenyl)thioureas

Article abstract of DOI:10.1016/j.molstruc.2017.03.113

The 1-(isomeric methylbenzoyl)-3-(4-trifluoromethylphenyl)thioureas (1–3) have been synthesized using the reaction of 2-methylbenzoyl isothiocyanate, 3-methylbenzoyl isothiocyanate and 4-methylbenzoyl isothiocyanate with 4-aminotrifluorotoluene in dry tet

Full text of DOI:10.1016/j.molstruc.2017.03.113

Accepted Manuscript
Synthesis, structural characterization and quantum chemical calculations on 1-
(isomeric methylbenzoyl)-3-(4-trifluoromethylphenyl)thioureas
Lei Qiao, Yu Zhang, Wei Hu, Jiajia Guo, Wenli Cao, Zimei Ding, Zhiwei Guo, An Fan,
Jirong Song, Jie Huang
PII:
S0022-2860(17)30418-0
10.1016/j.molstruc.2017.03.113
MOLSTR 23609
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 10 March 2017
Revised Date: 30 March 2017
Accepted Date: 30 March 2017
Please cite this article as: L. Qiao, Y. Zhang, W. Hu, J. Guo, W. Cao, Z. Ding, Z. Guo, A. Fan, J. Song,
J. Huang, Synthesis, structural characterization and quantum chemical calculations on 1-(isomeric
methylbenzoyl)-3-(4-trifluoromethylphenyl)thioureas, Journal of Molecular Structure (2017), doi: 10.1016/
j.molstruc.2017.03.113.
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Graphical abstract: The three novel isomeric acyl thiourea compounds were firstly prepared and
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characterized by some spectroscopic techniques. The molecular structure of compounds 1 and 3 was
determined by X-ray diffraction analysis. A detailed analysis of the intermolecular contacts in the
compounds 1 and 3 have been performed based on the Hirshfeld surfaces, their 2D fingerprint plots and the
enrichment ratios. Conformational aspects are also discussed in terms of the vibrational spectra.

Synthesis, structural characterization and quantum chemical calculations on
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1-(isomeric methylbenzoyl)-3-(4-trifluoromethylphenyl)thioureas
Lei Qiaoa, Yu Zhanga, Wei Hua, Jiajia Guoa, Wenli Caoa, Zimei Dinga, Zhiwei Guoa, An Fana, Jirong Songb and Jie Huanga,*
a School of Chemical Engineering, Northwest University/Shaanxi key Laboratory of Physico-Inorganic Chemistry, Xi’an,
Shaanxi 710069, People’s Republic of China
b Ministry of science and technology, The Palace Museum, Beijing 100009, People’s Republic of China
Abstract: The 1-(isomeric methylbenzoyl)-3-(4-trifluoromethylphenyl)thioureas (1-3) have been
synthesized using the reaction of 2-methylbenzoyl isothiocyanate, 3-methylbenzoyl isothiocyanate and
4-methylbenzoyl isothiocyanate with 4-aminotrifluorotoluene in dry tetrahydrofuran in good yields. The
series of compounds were characterized by FT-IR and Raman (vibrational spectra), multinuclear (1H and 13C)
NMR, mass spectrometry and elemental analyses techniques. Structural and conformational properties of
compounds 1 and 3 were determined by the X-ray single crystal diffraction. A detailed analysis of the
intermolecular actions in the two crystal structures has been performed based on the Hirshfeld surfaces and
their two-dimensional fingerprint plots. Different hydrogen bonds were formed in the compounds 1 and 3,
which have important impact to the FT-IR spectrum. In addition, vibrational spectral characteristics of
compounds 1-3 have been studied by FT-IR and Raman, along with the quantum chemical calculations at the
B3LYP/6-311++G (d, p) level of approximation.
Keywords: 1-(isomeric methylbenzoyl)-3-(4-trifluoromethylphenyl)thioureas; X-ray single crystal analysis;
Quantum chemical calculation; Hydrogen bonds; Hirshfeld surface
1. Introduction
Acyl thiourea derivatives have become the center of attraction to the scientific community for a widely
diversity applications [1] such as antiviral [2, 3], antimicrobial [4-6], anti-HIV [7], herbicidal [8], antitumor
[9, 10], anti-inflammatory [11], insecticidal [12] and fungicidal properties [13]. Furthermore, it can also be
used in heterocyclic syntheses [14-17] and anion recognition materials [18-20]. In addition, thiourea
derivatives are exceptionally versatile ligands in Coordination Chemistry [21], able to coordinate with the
transition metals such as Ni(ꢀ), Cu(ꢀ), Co(ꢀ), Fe(ꢁ) [22, 23], Zn(ꢀ) [24], Pd(ꢀ) [25] and Ru(ꢀ) [26]
ions as neutral monobasic or dibasic ligands.
Very recently, thiourea derivatives are placed at a prestigious status as evidenced by the fact that the
* Corresponding author. Tel: +86 029 88307755
E-mail address: huangjie@nwu.edu.cn

molecular structure of the class of compounds prior to their use in various applied fields [1]. M.G. Woldu et
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al. [27] demonstrated that the four main forms of acyl thiourea derivatives can be denoted as S, U, M and Z,
which the letters reflect the position of the C=O and C=S double bonds relative to the drawn N-H bond.
Aamer Saeed et al. [28] and Raúl Ramos Cairo et al. [29] also pronounced that Hirshfeld surfaces analysis is
an impressive tool for evaluating intermolecular interaction in a series of thioureas compounds. It is note
that the emergence of quantum chemistry does accelerate the study process of molecular structure. The
quantum chemistry method is one of most effective means to explain molecular structure such as the
infrared spectrum and raman activity [30-33], maximum absorption bands of UV-Vis [34], structure
1
parameters and downfield and upfield of H and 13C chemical shifts [35]. Furthermore, the electronic
properties which were calculated by the quantum chemistry can well explain the structure-activity
relationship of organic compounds [36]. Gil et al. performed thermodynamic [37] and non-linear optical
(NLO) behavior [38] for thiourea derivatives using the density functional method (DFT) with different basis
sets. Aamer Saeed et al. [39, 40] calculated the electronic and reactivity properties of thiourea compounds
by the natural bond orbital analysis using the quantum chemical calculation.
Many reports on 1-(acyl/aroyl)-3-(2-, 3- and 4-substituted alkyl/ aryl)thioureas can be found in the
literatures [32ꢂ35, 41]. Less attention, however, has been received by the isomeric 1-(2-, 3- and
4-substituted aroyl)-3-(alkyl/aryl)thioureas. Herein we report the preparation and spectroscopic and
conformational properties of 1-(isomeric methylphenyl)-3-(4-trifluoromethylphenyl)thioureas. In this article,
two crystal structures have been determined by X-ray diffraction. The intermolecular contacts have been
preformed based on the Hirshfeld surfaces and their associated 2D fingerprint plots. The FT-IR, Raman,
mass spectra and NMR spectroscopic properties were determined and discussed. We also validated the
FT-IR and Raman and analyzed those properties by the quantum chemical calculations using GAUSSIAN
09W program [42].
2. Experimental
2.1. Materials and measurements
The solvent tetrahydrofuran, ethyl acetate, N, N - dimethyl formamide (DMF), dichloro sulfoxide and
ethanol were of analytical grade quality and were used without further purification (E. Merck). The reagents
potassium thiocyanate, 4-aminotrifluorotoluene, 2-methylbenzoic acid, 3-methylbenzoic acid and
4-methylbenzoic acid were purchased from Aldrich and were of analytical grade and used as received.
Microwave syntheses were carried out using a BILON-CW-1000 microwave synthesizer with the
appropriate absorption power settings. Melting points were recorded using a Cossim KER3100-08S

apparatus and were uncorrected. Elemental analyses were conducted using an ELEMENTAR Vario EL
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elemental analyzer. 1H and 13C nuclear magnetic resonance (NMR) spectra were determined in
dimethylsulfoxide-d6 at 400 MHz and 100 MHz using a Bruker spectrophotometer. 1H NMR (400 MHz):
13
internal standard solvent DMSO-d6 (2.50 ppm from TMS): internal standard TMS; C NMR (100 MHz):
internal standard solvent DMSO-d6 (39.96 ppm from TMS): internal standard TMS; the splitting of proton
1
resonances in the reported H NMR spectra were remarked as s=singlet, d=double, t=triplet dd=doublet of
doublets, dt=doublet of triplets and m=multiple; coupling constants are reported in Hz. Mass spectra were
recorded on a MAT-112-S spectrometer at 70 eV.
2.2. Synthesis and characterization
A solution of prepared heterogeneous methyl benzoyl chloride (1.32-1.35 ml, 10 mmol) in dry
tetrahydrofuran (40 mL) was added drop wise to a three-necked round-bottomed flask containing potassium
thiocyanate (1.4577 g, 15 mmol). The mixtures were refluxed for approximately 2 hours at 60 . A solution
of 4-aminotrifluorotoluene (1.5307 g, 9.5 mmol) in tetrahydrofuran (20 mL) was added and reacted in
microwave heating 60-65 for about 90 seconds. The resulting mixture was pushed into 500 mL water and
filtered off, washed with ethanol and dried in vacuo. The forming compounds were grown at room
temperature from organic solvent (acetonitrile and ethyl acetate) for single crystals of compounds 1 and 3,
respectively.
2.2.1. Synthesis of 1-(2-methylphenyl)-3-(4-trifluoromethylphenyl)thiourea, (1)
White solid; Yield: 83.49%; m.p.: 187.8-188.1 ; FT-IR (KBr): v, cm-1 3355 (w, free N-H), 3154 (w,
assoc H-N), 2919 (w, Ar-CH), 1681 (s, C=O), 1158 (m, vs(NCN)), 763 (m, C=S). 1H NMR (400 MHz,
DMSO-d6): δ, ppm 12.69 (s, 1H, NH), 11.87 (s, 1H, NH), 7.99 (d, J=8.4 Hz, 2H, Ar-H), 7.80 (d, J=8.6 Hz,
2H, Ar-H), 7.58-7.41 (m, 2H, Ar-H), 7.31 (t, J=7.6 Hz, 2H, Ar-H), 2.44 (s, 3H, CH3). 13C NMR (100 MHz,
DMSO): δ, ppm 179.94 (C=S), 170.92 (C=O), 136.61 (Ar-C), 134.34 (Ar-C), 131.53 (Ar-C), 131.14 (2C),
128.68 (2C), 126.25 (Ar-C), 126.03 (m, 2C), 125.05 (2C), 123.23 (CF3), 19.96 (CH3). Anal. Calc. for
C16H13F3N2OS (MW=338.35) in wt%: C, 56.80; H, 3.87; N, 8.28. Found: C, 56.82; H, 3.79; N, 8.30. EI MS
(70 eV) m/z: 338.41 [M] +.
2.2.2. Synthesis of 1-(3-methylphenyl)-3-(4-trifluoromethylphenyl)thiourea, (2)
Pale yellow solid; Yield: 80.69%; m.p.: 114.6-116.4 ; FT-IR (KBr): v, cm-1 3357 (w, free N-H), 3246
(w, assoc H-N), 2922 (w, Ar-CH), 1666 (s, C=O), 1154 (m, vs(NCN)), 772 (m, C=S). 1H NMR (400 MHz,
DMSO-d6): δ, ppm 12.77 (s, 1H, NH), 11.67 (s, 1H, NH), 7.97 (d, J=8.4 Hz, 2H, Ar-H), 7.80 (dd, J=17.7,
9.2 Hz, 2H, Ar-H), 7.46 (dt, J=15.1, 7.6 Hz, 2H, Ar-H), 2.40 (s, 3H, CH3). 13C NMR (100 MHz, DMSO): δ,

ppm 179.94 (C=S), 168.73 (C=O), 142.15 (Ar-C), 138.33 (Ar-C), 134.32 (Ar-C), 132.39(2C), 129.64 (2C),
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128.87 (Ar-C), 126.29 (m, 2C), 125.10 (2C), 123.22 (CF3), 21.28 (CH3). Anal. Calc. for C16H13F3N2OS
(MW=338.35) in wt%: C, 56.80; H, 3.87; N, 8.28. Found: C, 56.79; H, 3.82; N, 8.25. EI MS (70 eV) m/z:
338.39 [M] +.
2.2.3. Synthesis of 1-(4-methylphenyl)-3-(4-trifluoromethylphenyl)thiourea, (3)
White solid; Yield: 79.70%; m.p.: 154.9-156.5 ; FT-IR (KBr): v, cm-1 3351 (w, free N-H), 3208 (w,
assoc H-N), 2931 (w, Ar-CH), 1679 (s, C=O), 1158 (m, vs(NCN)), 766 (m, C=S). 1H NMR (400 MHz,
DMSO-d6): δ, ppm 12.81 (s, 1H, NH), 11.63 (s, 1H, NH), 7.99-7.91 (m, 4H, Ar-H), 7.79 (d, J=8.59 Hz, 2H,
Ar-H), 7.36 (d, J=8.06 Hz, 2H, Ar-H), 2.40 (s, 3H, CH3). 13C NMR (100 MHz, DMSO): δ, ppm 179.98
(C=S), 168.48 (C=O), 144.24 (Ar-C), 142.16 (Ar-C), 129.55 (Ar-C), 129.51(2C), 129.32 (2C), 126.78
(Ar-C), 126.23 (m, 2C), 125.03 (2C), 123.22 (CF3), 21.63 (CH3). Anal. Calc. for C16H13F3N2OS
(MW=338.35) in wt%: C, 56.80; H, 3.87; N, 8.28. Found: C, 56.78; H, 3.78; N, 8.29. EI MS (70 eV) m/z:
338.34 [M] +.
2.3. Vibrational spectroscopy
Solid-phase infrared spectra (KBr pellets) were recorded in the 4000-400 cm-1 range on a Bruker
EQUINOX 55 FT-IR spectrometer. The FT-Raman spectra were recorded in the region 2000-100 cm-1 using
a Bruker IFS 66v spectrometer equipped with Ar+ laser source operating at 514.5 nm line with of spectral
width 2 cm-1.
2.4. Quantum chemical calculations
Quantum chemical calculations were performed with the GAUSSIAN 09W program package by using
the B3LYP DFT hybrid methods. The files of X-ray structure were sever as the initial geometry and fully
optimized for compounds 1 and 3. The conformational analysis of compound 2 also was performed around
all bonds having free rotation to obtain the most stable conformer [36]. The valence triple-ξ basis set
augmented with diffuse and polarization functions in both the hydrogen and heavy atom [6-311++G (d, p)]
were applied to optimize geometry parameter and to calculate frequency [43]. The Raman activities (in
Å
4/amu) calculated with the GAUSSIAN 09W program was converted to corresponding Raman intensities.
The calculated vibrational properties corresponding in all cases to potential energy minima for which no
imaginary frequency was found.
2.5. X-ray data collection, structure solution and refinement
Single crystal X-ray experiments were performed with Mo Kα radiation (λ=0.071073 nm) with Bruker
APEX-II CCD diffractometer. SHELXS 97 was used for structure solution and refinement using the direct

methods [44]. All the non-hydrogen atoms were obtained by the full-matrix-block least-squares method on
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F2 with anisotropic thermal parameters [45]. The hydrogen atoms were located in difference Fourier maps
and refined at idealized positions riding on the relevant carbon or nitrogen atoms with C-H=0.095 nm and
N-H=0.088 nm and with isotropic displacement Uiso(H)=1.2Ueq(C, N). All molecular plots and packing
diagrams were drawn using Diamond program [46] and additional metrical data were calculated using
PLATON [47]. The intermolecular contacts of compounds 1 and 3 were drawn in Fig. S1 using Mercury
program [48].
2.6. Hirshfeld surface computational method
Hirshfeld surfaces and their 2D fingerprint plots [49-52] were performed by the CrystalExplorer 3.1
software [53]. The Hirshfeld surface is becoming a valuable tool for decoding and quantifying the
intermolecular interactions in a whole-of-molecule approach [54-56]. The Hirshfeld surfaces analysis on
acyl thiourea derivatives were firstly reported by Aamer Saeed and coworkers [57], which is a quite big
breakthrough in the acyl thioureas field. In order to explore the intermolecular contacts and their types in a
molecule crystal, the dnorm (normalized contact distance) parameter were involved and defined for the follow
equation:
dnorm=(di- rvi dW )/ rivdW +(de+ revdW )/ rvedW
[58]
The parameters di and de were defined as the distances from the points on the surface to the nearest nucleus
inside and outside the surface, respectively. The rvdW is the van der Waals radius of the appropriate atom
internal or external to the surface. The red scale on the Hirshfeld surface (dnorm is negative)-white (dnorm is
equal to zero)-blue (dnorm is positive) was introduced to visualize the intermolecular contacts. The 3D dnorm
surfaces were mapped over a fixed color of -0.27 (red) to 1.2 Å (blue). The fingerprint plots were displayed
by using the translated 0.8-3.0 Å range and including reciprocal contacts. The shape index was mapped in
the color range of -1.0 au (concave) to 1.0 au (concave) Å. The curvedness was mapped by default.
3. Results and discussion
3.1 Synthesis and characterization
The synthetic pathway to the title 1-(isomeric methylphenyl)-3-(4-trifluoromethylphenyl)thioureas is
shown in Scheme 1[59]. Those corresponding isomeric methyl benzoyl isothiocyanate were produced by
reaction of corresponding methyl benzoyl chloride with potassium thiocyanate in dry tetrahydrofuran. After
reaction, 4-aminotrifluorotoluene was added into three-necked round-bottomed flask to generate the title
compounds in 79.70%-83.49% yields. The products 1 and 3 were recrystallized with acetonitrile and ethyl

acetate to shape the crystal suitable for the X-ray crystal diffraction, respectively.
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In the H NMR spectra of all synthesized thiourea compounds, the protons of the two -NH groups are
1
obtained as single peak at 12.69-12.81 ppm and 11.61-11.87 ppm, respectively. The protons of benzene rings
are observed at 7.31-7.99 ppm and the protons of methyl group appeared at 2.40-2.44 ppm in the title
compounds. In the 13C NMR spectra the characteristic phenyl signals are observed at δ 136.6-125.1,
142.2-125.1 and 144.2-125.0 for compounds 1, 2 and 3, respectively. The signals of the carbonyl and
thiocarbonyl are found around δ 179.94 and 170.92 for 1, δ 179.94 and 168.78 for 2, δ 179.98 and 168.48
for 3 as well. The carbons of trifluoromethyl groups are observed at 123.23 ppm in all compounds. The
FT-IR spectra of synthesized thioureas 1, 2 and 3 show intense and characteristic absorptions at 3355, 3357
and 3351 cm-1 for N-H(1), 3154, 3246 and 3208 cm-1 for H-N(2), 2919, 2922 and 2931 cm-1 for (C-H, Ph),
1523, 1521 and 1525 cm-1 for (C=C, Ph), 1107, 1104 and 1101 cm-1 for (C-F), at 1681, 1666 and 1679 cm-1
for the carbonyl, 763, 772 and 766 cm-1 for thiocarbonyl, respectively. The detail of vibrational spectra
would be discussed in the following part.
(1) 2-CH3, (2) 3-CH3, (3) 4-CH3
Scheme 1. Synthesis of 1-(isomeric methylphenyl)-3-(4-trifluoromethylphenyl)thioureas.
3.2. Molecular and crystal structure
Crystals of compounds 1 and 3 were grown by slow evaporation of acetonitrile and ethyl acetate at
room temperature, respectively. Data collections and structure refinement details are summarized in Table 1.
Some selected bond lengths, bond angles and dihedral angles are in normal ranges and comparable to those
in experiment data as shown in Table 2 together with the calculated values at the B3LYP level in gas. The
two crystal structures with atomic labeling and intramolecular hydrogen bonds are depicted in Fig. 1 and Fig.
2, respectively. The computed molecular structures are shown in Fig. 3. Intra- and intermolecular hydrogen
bond parameters are listed in Table 3. The X-ray result of the synthesized thiourea derivatives exhibit that 1
crystallized in triclinic system with space group of P-1, while 3 crystallized in orthorhombic system with

space group of Pbca. The unit cell dimensions for 1 and 3 are a=7.431(3) Å, b=7.762(4) Å, c=14.075(7) Å,
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α=100.619(9)°, β=96.159(8)°, γ=91.718(8)°, V=792.3(6) Å3 and Z=2; and a=6.622(2) Å, b=15.490(5) Å,
c=31.130(10) Å, α=β= γ=90°, V=3193.3(19) Å3 and Z=8, respectively.
The C8-S1 and C9-O1 bond lengths both show the expected double-bond character in two crystal
structures, which can be demonstrated using the quantum chemical calculation (see Fig. 3). The C9(O1)-N1,
C8(S1)-N1 and C8(S1)-N2 bond lengths indicate the partial double-bond character typical for this type of
compounds which are in good agreement with the report related trifluoromethyl substituted benzene species
[60-63]. Compared to the unsubstituted 1-benzoyl-3-phenylthioureas, the trifluoromethyl substitution at C4
does not result in any significant effect on these bond lengths which are consistent with the paper reported
[64]. The molecular structures of 1 and 3 which possess methyl group at different positions consist of similar
thiourea cores (-CONHCSNH-). The cores are mostly planar with O-C-N-C and C-N-C-S torsion angles of
2.759° and 174.942° for 1, 6.631° and 164.192° for 3 as well. The dihedral angle between the C2-C7 plane
and the C10-C15 plane are 13.50° and 37.75° for compounds 1 and 3, respectively. The compounds 1 and 3
of the corresponding angles with respect to the (N/C/S/N/C/O) plane are 47.82° and 69.59° for the C2-C7
plane and 60.78° and 34.16° for the C10-C15 plane, respectively. Dihedral angles between these carbonyl
thiourea planes and the phenyl rings with the methyl group measure for 1: 60.78° and for 3: 34.16°
, which
can be attributed to the effects of methyl group of steric hindrance.
Crystal packing patterns show intermolecular N-H···O hydrogen bonds for 1 (-x, 1-y, 1-z) and 3 (1-x,
1-y, 1-z), forming centrosymmetric dimmers, as shown in Figs. 4 and 5, with N-H···O contacts of 3.151(5)
and 3.162(5) Å, respectively. Meanwhile, intramolecular N-H···O hydrogen bonds form S (6) ring [65] and
contribute to the relative planarity of the acyl thiourea moieties in compounds 1 (Fig. 1) and 3 (Fig. 2). The
intermolecular hydrogen bonds linking X-H···S=C forms parallelograms in all two compounds. The crystal
packing of compound 1 is stabilized by N-H···S (1-x, -y, 1-z) hydrogen bonds, wherein atom S as an
acceptor forming R22 (8) ring as well as on compassion with the reported data for related molecules [33].
Noted that the intramolecular C-H···S hydrogen bonds in compound 1 form a S (6) rings and contribute to
the relative planarity of the acyl thiourea moieties, as is shown in Fig 1. The packing diagram of compound
3 shows the intermolecular C-H···S (-0.5+x, 1.5-y, 1-z) actions form R22 (12) motif, as is shown in Fig 5.
The C-H···π interactions were calculated using the PLATON program. The parameters of compound 1
are not satisfy with the conditions of C-H···π interactions. However, in the crystal packing patterns of
compound 3, the C-H···π interactions are formed between the H15 on the phenyl ring and the C2-C7 ring
with a symmetry code: 1-x, 1-y, 1-z. The distance of 2.98 Å between H15 and the centroid of C2-C7 ring is
content with the range the C-H···π interactions. The distance between H15 and the nearest carbon atom in

the phenyl ring is 3.612(5) Å (the detail parameters see Table S3).
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Table 1.
Data collections and structure refinement details for compounds 1 and 3.
Compound
Chemical formula
Formula weight
Temperature (K)
Wavelength (Å)
a (Å)
Compound 1
C16H13F3N2OS
338.34
Compound 3
C16H13F3N2OS
338.34
296(2)
296(2)
0.71073
7.431(3)
7.762(4)
14.075(7)
100.619(9)
96.159(8)
91.718(8)
792.3(6)
2
0.71073
6.622(2)
15.490(5)
31.130(10)
90
b (Å)
c (Å)
α (degree)
β (degree)
γ (degree)
90
90
Volume (Å3)
Z
3193.3(19)
8
Dc (Mg/m3)
Crystal system
Space group
Index ranges
1.418
1.408
Triclinic
P-1
Orthorhombic
Pbca
-8 ≤ h ≤ 8,
-9 ≤ k ≤ 5,
-16 ≤ l ≤ 15
0.240
-7 ≤ h ≤ 7,
-8 ≤ k ≤ 8,
-36 ≤ l ≤ 25
0.238
Absorption
Coefficient (ꢀ)
F (000)
348
1392
Theta range for data
collection (o)
1.48 to 25.09
1.31 to 25.10
Reflections collected
Independent reflections
R (int)
3968
14853
2793
2832
0.0226
0.0609
Goodness-of-fit on F2 (S)
R (all data)
1.020
1.051
R1 = 0.0951, wR2 = 0.1958
R1 = 0.1056, wR2 = 0.2324

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Fig. 1. Molecular structure of compound 1 in a single crystal at 296K (with the thermal ellipsoids shown at a 50%
probability level). Intramolecular N-H···O and C-H···S hydrogen bonds are shown as a light green dashed line.
Fig. 2. Molecular structure of compound 3 in a single crystal at 296K (with the thermal ellipsoids shown at a 50%
probability level). Intramolecular N-H···O hydrogen bond is shown as a light green dashed line.
Fig. 3. Computed molecular structures of 1 (left), 2 (middle) and 3 (right).
Table 2.
Selected bond lengths [Å] and angles [o] for compounds 1 and 3. Computed values at the B3LYP/6-311++G (d, p) level of
approximation for compounds 1, 2 and 3.
Compound
Parameter
1
2
3
Experimental
Calculated
Calculated
Experimental
Calculated
Bond distances

C8=S1
1.643(4)
1.213(4)
1.421(4)
1.344(4)
1.390(4)
1.380(4)
1.669(3)
1.669(7)
1.669(4)
1.218(5)
1.436(5)
1.337(5)
1.389(5)
1.391(5)
1.670(1)
1.229(3)
1.407(1)
1.350(8)
1.409(6)
1.383(5)
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C9=O1
1.227(9)
1.228(8)
1.407(2)
1.350(9)
1.410(1)
1.382(8)
N1-C5
1.407(5)
1.351(3)
1.410(6)
1.385(3)
N1-C8
N2-C8
N2-C9
Bond angles
N1-C8=S1
N1-C8-N2
N2-C8=S1
N2-C9=O1
Dihedral angles
126.1(3)
115.0(3)
118.8(2)
123.1(3)
129.6(6)
113.5(1)
116.8(3)
122.3(4)
129.6(7)
113.5(6)
116.7(6)
122.3(6)
124.9(3)
117.3(4)
117.8(3)
121.9(4)
129.6(4)
113.5(8)
116.7(8)
122.2(4)
S1=C8-N2-C9 174.942(31)
178.471(87)
4.692(68)
179.252(46)
3.837(67)
164.192(33)
6.631(65)
179.204(56)
3.782(83)
O1=C9-N2-C8 2.759(62)
Table 3.
Hydrogen bonds for compounds 1 and 3 [Å and o].
Compound
Donor-Hydrogen··· Acceptor
N1-H1···O1
D-H (Å)
0.8600
0.8600
0.9300
0.8600
0.8600
0.8600
0.9300
H···A (Å)
1.9700
2.4700
2.8600
2.7100
2.4700
2.0800
2.7800
D··· A (Å)
D-H···A (°)
2.665(4)
3.151(5)
3.231(4)
3.651(4)
3.162(5)
2.707(5)
3.593(5)
137.000
137.000
105.000
172.000
138.000
130.000
146.000
1
N1-H1···O1a
C6-H6···S1
N2-H2···S1b
N1-H1···O1c
3
N1-H1···O1
C11-H11···S1d
Symmetry equivalent position: (a) -x, 1-y, 1-z; (b) 1-x, -y, 1-z; (c) 1-x,1- y, 1-z; (d) -1-x, 1.5+y, 1.5-z.
(a) (b)

ACCEPTED MANUSCRIPT
Fig. 4. Packing diagrams of the compound 1; (a) viewed along the a axis; (b) viewed along the b axis.
Fig. 5. Packing diagram of the compound 3 viewed along the a axis.
3.3. Hirshfeld surface analysis
The Hirshfeld surfaces and their two-dimensional fingerprint plots were performed for the purpose of
analyzing and quantizing structure properties in relation to packing patterns. The geometric parameters of
hydrogen bonds for compounds 1 and 3 are listed in Table 3.
The intermolecular contacts of compounds 1 and 3 were analyzed using the Hirshfeld surfaces, which
are shown as Fig. 6. The dnorm map of compounds 1 and 3 show a pair of adjacent deep-red regions (labeled
1) which demonstrate the strong N-H···O hydrogen bonds (Table 3) forming R22 (12) dimers in the
corresponding crystal packing patterns (Fig. 4(a) and Fig. 5). The compound 1 also exhibit red regions close
to both sulfur atom and hydrogen atom (labeled 2), as a result of N-H···S hydrogen bond forming R22 (8)
loops, such as illustrated in the Fig. 4(a) and discussed in the crystal packing analysis. It is noted that the
intermolercular contacts are formed by the C=S group with the C-H of the benzene ring instead of the N-H
group in the compound 3 (labeled 2). Meanwhile, as can be seen in the compound 3 the red regions occur
near to the S atom, which is due to form bifurcate C-H···S hydrogen bonds (labeled 3 and 4). Differently,

when we look at to the Hirshfeld surface of compound 1 again, it is observed that the S atom and the C atom
ACCEPTED MANUSCRIPT
of the benzene ring is involved in a C···S intermolecular contact (labeled 4), resulting in a red color in the
Hirshfeld surface. In addition, the compound 1 also show red regions near to both the F atom and the H atom
of methyl, which is form the F···H intermolecular contact (labeled 3).
Their 2D fingerprint plots of the main intermolecular contacts for compounds 1 and 3 are depicted in
Fig. 7. Although the structure 1 is very similar to the structure 3, the fingerprint plots are quite different (Fig.
7A). The H···H contact of compound 3 shows a sharper spike (labeled 1 in Fig. 7A) centered near a sum of
2.3
O···H (labeled 2 in Fig. 7A) and S···H (labeled 3 in Fig. 7A) intermolecular contacts are a pair of sharp
spikes with a center near a sum of 2.3 and 2.5 (di+de) for compound 1, 2.3 and 2.6 (di+de) for compound
Å (di+de) than the spike centered near a sum of 2.4 Å (di+de) for compound 1 (labeled 1 in Fig. 7A). The
Å
Å
3, correspond to N-H···O and N-H···S hydrogen bonds for compound 1, N-H···O and C-H···S hydrogen
bonds for compound 3, respectively. The F···H contact have a pair of spikes attached to the O···H contact,
which is centered near a sum of 2.5 and 2.6
Å (di+de) for compounds 1 and 3, respectively. In addition, the
hydrophobic intermolecular contacts (C···H and C···C) are shown in Fig. 7C and Fig. 7D. Hence, the intra-
and intermolecular hydrogen bonds together with the hydrophobic intermolecular contacts provide forces for
self-assembly in the compounds 1 and 3.
The two molecular surfaces connecting each other in crystals can be explained by complementary
hollows (red) and bumps (blue) on the Shape index. The planar stacking arrangements must meet the
condition of the relatively flat surface (green) on curvedness [58]. In the curvedness for compounds 1 and 3,
they all meet the condition of the relatively flat surfaces. However, there do not show the complementary
hollows and bumps in phenyl regions of Shape index of compounds 1 and 3 in Fig. 8. So the π-π stacking
interactions do not exist.
The enrichment ratios of the main intermolecular contacts were calculated using the method reported
by C. Jelsch and coworkers [66]. The result of the enrichment ratios for compounds 1 and 3 are shown in
Table 4 (complete information is provided in Table S1). It is noted that the H···H intermolecular contacts
are lightly impoverished in compounds 1 (EHH=0.78) and 3 (EHH=0.88) with the percentage of RHH being
32.83% for compound 1 and 32.60% for compound 3, respectively, which is quite different with the reported
paper [28]. Meanwhile, it is observed that the O···H, S···H, F···H and C···H contacts are highly favored for
compounds 1 and 3, with the enriched ratio of EOH, ESH, EFH and ECH being 1.49, 1.35, 1.49 and 1.03 for
compound 1 and 1.44, 1.37, 1.24 and 0.96 for compound 3, respectively. The high values of EOH, ESH, EFH
and ECH and are helpful for explaining that the H···H intermolecular contacts are lightly impoverished in
compounds 1 and 3, which is because H···H, O···H, S···H, F···H and C···H contacts are presumably in

competition. There is an obvious difference that the N···H intermolecular contacts in the compounds 1 and 3
ACCEPTED MANUSCRIPT
have a great gap in the value of ENH. More concretely, the N···H intermolecular contact is slightly favoured
for compound 1 (ENH=0.92) and impoverished for compound 3 (ENH=0.47). This fact demonstrated the ENH
ratios and the corresponding random contacts do not remain relativity, which consist with the reported
research [28]. Compound 1 and compound 3 have also the second difference in the F···F intermolecular
contacts. The F···F intermolecular contact has a highly enriched (EFF=1.43) for compound 3 but a slightly
impoverished for compound 1 (EFF=0.56). The third difference between compound 1 and compound 3 is that
the former have a highly enriched (ECS=1.31) but the latter have a slightly impoverished (ECS=0.68) in the
C···S contacts (Fig. S1). The C···C contacts are highly enriched (ECC=1.38) for compound 1 with the
percentage of RCC merely being 2.7, enriched (ECC=1.96) for compound 3 with the percentage of RCC only
being 4.3. The C···O contacts are very impoverished for compounds 1 (ECO=0.32) and 3 (ECO=0.32).
Compound 1
Compound 3
Fig. 6. Pictures of the Hirshfeld surface in two orientations for compounds 1 and 3 with thermal ellipsoids plotted at 50%
probability level. The right column is rotated by 180° around the horizontal axis of the plot. Number arrows are described

either in Table 3 or in the text.
ACCEPTED MANUSCRIPT
(A) The fingerprint plots H···H, O···H and S···H.
(B) The fingerprint plots F···H.
(C) The fingerprint plots C···H.

ACCEPTED MANUSCRIPT
(D) The fingerprint plots C···C.
Fig. 7. The fingerprint plots (A-D) for compounds 1 (left) and 3 (right). The numbers 1, 2 and 3 in the (A) represent H···H,
O···H and S···H intermolecular contacts, respectively. The pictures B, C and D show F···H, C···H and C···C
intermolecular contacts, respectively.
Compound 1 (A)

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Compound 1 (B)
Compound 3 (A)
Compound 3 (B)

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Fig. 8. Hirshfeld surfaces for compounds 1 and 3 mapped with shape index (the left column) and curvedness (the right
column). The letters “A” and “B” represent front and back views of the same group of molecules.
Table 4.
Enrichment ratios EXY of the main intermolecular interactions for compounds 1 and 3.
Interaction
H···H
C···H
N···H
O···H
S···H
1
3
0.78
1.03
0.92
1.49
1.35
1.49
1.38
0.32
1.31
0.56
0.88
0.96
0.47
1.44
1.37
1.24
1.96
0.08
0.68
1.43
F···H
C···C
C···O
C···S
F···F
* EXY value for random contacts RXY lower than 0.9% was not calculated.
3.4. 1H and 13C NMR spectra
1H NMR and 13C NMR spectra were determined in DMSO-d6 solution at 400 and 100 MHz,
respectively, using a Bruker spectrophotometer. All three thiourea compounds exhibit the corresponding
1
group characteristics in the same H NMR spectra (Fig. 9). The proton of C=O-N-H group of compound 1

1
(11.87 ppm) is at a lower field compared with compounds 2 (11.67 ppm) and 3 (11.63 ppm) in H NMR.
ACCEPTED MANUSCRIPT
Again the carbon of C=O group for compound 1 is at a lower field that is similar to their H NMR spectra
1
(Fig. 10). The protons of methyl group of compound 1 is at δ 2.44 ppm which is bigger that the shifts of
compounds 2 and 3. The shifts of the carbon of methyl groups are arranged in following order: (1) < (2) <
(3). The shifts of the proton and carbon of phenyl ring are different due to the different site of methyl group.
The isomerization has slight influence on the position of chemical shift from the view of the whole NMR
spectra which is in consistent with the conclusion reported by H.M. Abosadiya [35].
Fig. 9. The 1H NMR spectra of compounds 1, 2 and 3.

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Fig. 10. The 13C NMR spectra of compounds 1, 2 and 3.
3.5. Vibrational analysis
The vibrational spectra have a plenty of indistinguishable absorptions for the title compounds. In order
to explain clearly assignments of the observed infrared absorption, the theoretically calculated vibrational
analysis were performed using B3LYP/6-311++G (d, p). The geometric parameters are in good agreement
with the experimental ones (Table 2) and the computed harmonic frequencies are listed in Table 5.
In the infrared spectra broad absorptions are observed at 3355 cm-1 for compound 1, 3357 cm-1 for
compound 2, 3351 cm-1 for compound 3 which all could be assigned to the formation of C=O···H-N
intramolecular hydrogen bonds [67]. It noted that the infrared spectrum of compound 1 is quite different
from compounds 2 and 3 for which the spectrum 1 becomes wide in width and the spike generates a red shift
phenomenon at 3154 cm-1 (see Fig. S9). It also proves that the compound 1 forms the N-H···S=C (1-x, -y,
1-z) intermolecular hydrogen bond while the hydrogen bond do not be involved in compound 3. The
phenomena indicate that compound 2 is more similar with 3 in molecular conformation. But the
isomerization effect on virbration modes is negligible from the view of the whole FT-IR spectra that is also
in consistent with the conclusion reported by H.M. Abosadiya [35].
Fig. 11 shows the Raman and IR spectra of the title compound in the 2000-400 cm-1 range. Many
signals originate in both the central thiourea moiety and the substituent groups. The strong IR absorptions at
1681, 1666 and 1679 cm-1 for compounds 1-3, respectively, are assigned to the C=O stretching modes. Very

strong counterparts are observed in the Raman spectra at 1688, 1673 and 1679 cm-1 for the three compounds.
ACCEPTED MANUSCRIPT
Calculated frequencies for this mode are also very similar for the three isomers [1717 (1), 1714 (2) and 1713
(3)]. The relative low frequency value for υ(C=O) is in accordance with the formation C=O···H-N
intermolecular hydrogen bonds. In addition, this phenomenon also can be explained as being a result of
conjugated resonance interactions between the carbonyl and the phenyl ring in title compounds. It is noted
that the υ(C=O) modes appreciably couple with the C-N stretching modes and the N-H bending modes in the
similar compounds [31, 32].
The δ(N-H) ( ) deformation modes of the amide and thioamide group are expected to appear
absorptions in the 1600-1500 cm-1 range of the FT-IR spectrum. The FT-IR spectrum of the title compounds
appear a middle intense bands at 1523, 1521 and 1525 cm-1 for compounds 1, 2 and 3, respectively, which
are assigned as δ(N1-H). The Raman spikes correspond to middle intense signals at 1528, 1528 and 1526
cm-1, respectively. Meanwhile, the most intense infrared absorptions appear at 1501 and 1503 cm-1 for
compounds 1 and 3, which are assigned as δ(N2-H). The calculated values at δ(N1-H) and δ(N2-H) at 1600
and 1539 cm-1 for 1, 1601 and 1542 cm-1 for 2, 1599 and 1534 cm-1 for 3 are in good agreement with the
experiment values.
In the region between 1400 and 1100 cm-1 in the FT-IR spectra of the title compounds contains some
medium intensity absorptions from skeletal motions, especially including the vibrations of υ(C-N) in the
thiourea cores. Due to the vibrational properties reported for the similar compounds, it is expected to appear
in the 1400-1300 cm-1 region for symmetric and antisymmetric stretching modes of C-N. The NCN
antisymmetric stretching modes for the thiourea moiety (thioamide bandꢀ) is assigned at 1312, 1324 and
1312 cm-1 for compounds 1-3, respectively, which is in good agreement with the Raman values. Computed
values are 1369, 1371 and 1373 cm-1, which are slightly higher than the experiment, by using the
B3LYP/6-311G++ (d, p) level. The symmetric υas(NCN) stretching mode (thioamide band ꢁ) is assigned at
1158, 1154 and 1158 cm-1 for compounds 1-3, respectively. The Raman counterparts are observed as signals
of intensities of 1167, 1163 and 1161 cm-1, respectively.
It is worthy to note that weak FT-IR absorptions centered at 763, 772 and 766 cm-1 with weak intensity
Raman signals are assigned to the υ(C=S) modes for compounds 1-3, respectively, in good agreement with
the calculated values (see band ꢃ of Fig. 11). The formation of C=S···H-X intermolecular hydrogen bonds
seems to deeply affect the frequency of the υ(C=S) modes compared with the related report which υ(C=S) is
assigned to the absorption appeared at 1325 cm-1 [68].
The norm modes associated with the υ(C-H) and υ(C=C) stretching vibrations of the phenyl rings are

observed in the typical range with values located in the 3050-2850 cm-1 and below 1600 cm-1, respectively.
ACCEPTED MANUSCRIPT
The C-F stretching vibrations are observed at 1107, 1104 and 1101 cm-1, which are in good agreement with
the calculated values.
Fig. 11. FT-IR (the dashed lines) and FT-Raman (the solid lines) spectra for compounds 1, 2 and 3 in the 2000-400 cm-1
region.
Table 5
Experimental and theoretical (B3LYP/6-311++G**) vibrational data (cm-1) with a tentative assignment for the title
compounds.
FTIRa
FT-Ramana
Calculatedb
Proposed
assignment
approximate
descriptionc
ν(N2-H)
1
2
3
1
2
3
1
2
3
3355 vw 3357 w 3351 w
3154 m, 3246 3208 sh
3607(42.0)
3612(39.9)
3616(38.4)
3328(406.3) 3322(418.8) 3319(431.2) ν(N1-H)
br
m
3025w
3036 w 3071 w
3240(11.1)
3201(1.0)
3239(10.9)
3202(1.0)
3240(11.0)
3202(1.0)
ν(C-H)
ν(C-H)
2919 vw 2922
m
2931vw
2849 vw 2851 w 2848 vw
3198(1.1)
3198(1.1)
3198(1.1)
ν(C-H)

1681 s
1666 s 1679 s
1603 s 1611 s
1688 s
1619 w
1594 w
1673 s 1679 s 1717(121.1) 1714(94.0)
1713(103.9) ν(C=O)
1660(32.0) ν(C-C)
ACCEPTED MANUSCRIPT
1617 w 1617 w 1660(37.3)
1660(35.4)
1594 m
1586
m
1592 m
1591 w
1648(556.9) 1649(376.9) 1644(645.1) ν(C-C)
1600(326.8) 1601(323.9) 1599(373.3) δ(N2-H)
1539(412.3) 1542(372.9) 1534(219.6) δ(N1-H)
1523 vs 1521 s 1525 s
1528 m
1528
m
1526
m
1501 vs
1408 m
1513 vs
1405 m
1417
m
1446(24.0)
1445(23.9)
1447(24.3)
ν(C-C)
1312 vs 1324 s 1312 s
1326 w
1329 w 1327 w 1369(545.1) 1371(592.8) 1373(630.6) νas (N-C-N)
1277(117.9) 1286(131.5) 1282(150.8) ν(C8-C2)
1259 m, 1272
sh
1256 m
m
1243 m, 1246
sh
1244 m
1243 s
1247 s 1238 s 1259(7.2)
1262(2.9)
1250(26.9)
δ(C-H)
1158 vs 1154 s 1158 vs
1167 w
1163 w 1161 w 1170(163.8) 1162(288.6) 1165(267.9) νs(N-C-N)
1120(119.8) 1121(28.0) 1121(133.0) ν(C-F)
1107 s
1064 s
1015 m
962 w
1104
vs
1101 vs
1069 s 1063 s
1066 m
1018 w
1067
m
1066m 1076(189.2) 1076(197.4) 1087(12.7)
ν(C=S)/
νs(CNC)
δ(CCC)
1014
m
1017 m
1017 w 1019 w 1028(49.8)
1028(48.8)
1028(51.8)
953 w
923 w
890 w
837 s
961 w
934 w
866 m
841s
972(4.2)
969(0.8)
967(5.7)
970(3.0)
968(0.7)
872(8.2)
864(75.6)
756(20.4)
702(2.0)
689(6.9)
δ(N-C7-N)
δ(C-H)
941 m
866 w
932 m 936 m
868 w
968(0.6)
873(11.2)
864(82.8)
774(20.8)
718(0.5)
692(4.9)
861m
840 m
763 s
δ(NC=O)
δ(C-H)
837 m
863(84.2)
774(28.2)
772 m 766 s
715 m
724 w
676 w
730 w
684 w
727 w
ν(C=S)
705 m
ρ(C-H)
675 m, 686 m, 678m
696(10.0)
ρ(C-H, Ph)
sh
sh
650 m
632 m
618 m
660 m 660 m
652 w
631 w
619 m
658 w
628 w
659 w
636 w
670(49.1)
661(38.9)
610(7.5)
670(21.2)
644(37.2)
607(9.5)
654(6.0)
ρ(N2-H)
δ(C=O)
oop(C=S)
ρ(C-H)
629 w
611 m
636 m
610 m
592 m,
sh
638(41.4)
614(14.4)
606(20.4)
612 m 608 m
600 s, sh 590
s,sh
593(12.1)
593(13.6)
557vw
551 w
549 w, 547 m
546 m 546 m
555(0.4)
513(6.7)
569(0.5)
514(9.4)
564(1.5)
513(5.8)
ρ(C-H)
δ(CCC)
sh
510 w
452 w
507 w, 506 w
sh
505 w
505 w
492 w
498 w
503(3.0)
462(2.2)
378(2.2)
334(18.8)
196(0.9)
508(2.5)
462 (9.5)
366(0.4)
339(28.0)
195(1.2)
490(6.9)
443(9.1)
360(11.5)
335(14.0)
196(0.9)
ρ(C-H)
δ(CCC)
δ(SCN)
δ(CCC)
ρ(NCS)
451 w
365 m
365 m 365 m
314 w
312 w
311 w
190 s
190 s
190 s
a FT-IR of solid in KBr pellets, FT-Raman of finely powered solid. Bind intensity: vs = very strong, s = strong, m = medium,
w = weak, vw = very weak, sh=shoulder bond.
b Scaled computed values for S form. In parentheses relative bond strengths IR intensities [in km/mol].
c v: stretching (subscripts s and as refer to symmetric and antisymmetric modes, respectively), δ: deformation, ρ: rocking,
oop: out of plane deformation modes.

4. Conclusion
ACCEPTED MANUSCRIPT
Three novel 1-(isomeric methylbenzoyl)-3-(4-trifluoromethylphenyl)thioureas have been synthesized
and fully determined by spectroscopy techniques. The structural and conformational properties of
compounds 1 and 3 were determined by the X-ray single crystal diffraction. The Hirshfeld surfaces,
fingerprint plots and the enrichment ratios were carried out to clearly explain the intermolecular interactions
and their quantitative contributions to the crystal packing of the two thiourea compounds. The FT-IR spectra
revealed that the structure 2 is more similar with structure 3 rather than structure 1 by comparing to the
value of wavelength. And the isomerization effect has slight effect on the whole FT-IR and NMR spectra.
The main normal modes have been analyzed by the joint analysis of the FT-IR spectra, the Raman spectra
and the corresponding calculated values.
Acknowledgements
This work is funded by the Science and Technology Program of Shaanxi Province, China
(No.2013K02-25), the Science and Technology Program of Xi’an, China (No.NC1404) and the Science and
Technology Research and Development Program of Shaanxi Province, China (No.14JF025).
Appendix A. Supplementary material
Crystallographic data for the structures reported in this paper have been deposited with Cambridge
Crystallographic Data Center as supplementary publication nos. CCDC 1517869 for 1 and CCDC 1519303
for 3. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK, (fax: +44 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).” Other supporting
materials can be found in the Electronic Supplementary Material of this paper.
References
[1] A. Saeed, R. Qamar, T.A. Fattah, U. Flörke, M.F. Erben, Res. Chem. Intermed. 42 (2016) 1-41.
[2] B. Lal, A. Badshah, A.A. Altaf, N. Khan, S. Ullah , Appl. Organomet. Chem. 25 (2011) 843-855.
[3] M.J. Di Grandi, K.J. Curan, G. Feigelson, A. Prashad, A.A. Ross, R. Visalli, J. Fairhurst, B. Feld, J.D.
Bloom, Bioorg. Med. Chem. Lett. 14 (2004) 4157-4160.
[4] M.K. Rauf, A. Talib, A. Badshah, S. Zaib, K. Shoaid, U. Floerke, U. Imtiazed-Din, J. Iqbal, Eur. J. Med.
Chem. 70 (2013) 487-496.
[5] A. Saeed, U. Shaheen, A. Hameed, S.Z. Haider Naqvi, J. Flour. Chem. 130 (2009) 1028-1034.

[6] S. Saeed, N. Rashid, P.G. Jones, M. Ali, R. Hussain, Eur. J. Med. Chem. 45 (2010) 1323-1331.
ACCEPTED MANUSCRIPT
[7] T.K. Venkatachalam, C.Mao, F.M. Ucku, Bioorg. Med. Chem. 12 (2004) 4275-4284.
[8] X. Sijia, D. Liping, K. Shaoyong, J. Liangbin, Chem. J. Internet 5 (2003) 60-70.
[9] A. Bielenica, J. Stefańska, K. Stępień, A. Napiórkowska, E. Augustynowicz-Kopeć, G. Sanna, S.
Madeddu, S. Boi, G. Giliberti, M. Wrzosek, M. Struga, Eur. J. Med. Chem. 101 (2015) 111-125.
[10] M. K. Rauf, S. Zaib, A. Talib, M. Ebihara, A. Badshah, M. Bolte, J. Iqbal, Bioorg. Med. Chem. 24
(2016) 4452-4463.
[11] M. Amir, H.S. Kumar, Eur. J. Med. Chem. 43 (2008) 2056-2066.
[12] B. Wang, Y. Ma, L. Xiong, Z. Li, Chin. J. Chem. 30 (2012) 815-821.
[13] S. Saeed, N. Rashid, P. G. Jones, R. Hussain, M. H. Bhatti, Cent. Eur. J. Chem. 8 (2010) 550-558.
[14] D.Anshu, A. Kapil, S. Meha, Synth. Commun. 34 (2004) 1141-1155.
[15] A. Saeed, S.U. Mahmood, M. Rafiq, Z. Ashraf, F. Jabeen, S.Y. Seo, Chem. Biol. Drug Des. 87 (2016)
434-443.
[16] U. Heinelt, D. Schultheis, S. Jager, M. Iindenmaire, A. Pollex, H. S.G. Beckmann, Tetrahedron 60
(2004) 9883-9888.
[17] A. Saeed, U. Flörke, M.F. Erben, J. Sulfur Chem. 35 (2014) 318-355.
[18] Y. Zhang, J. Qin, Q. Lin, T. Wei, J. Flour. Chem. 38 (2006) 1222-1227.
[19] S.I. Kondo, M. Nagamine, Y. Yano, Tetrahedron Lett. 44 (2003) 8801-8804.
[20] J.L. Wu, Y.B. He, Z.Y. Zeng, L.H. Wei, L.Z. Meng, T.X. Yang, Tetrahedron 60 (2004) 4309-4314.
[21] K.R. Koch, Coord. Chem. Rev. 216-217 (2001) 473-488.
[22] H. Mandal, D. Ray, Inorg. Chim. Acta. 414 (2014) 127-133.
[23] N. Selvakumaran, A. Pratheepkumar, S.W. Ng, E.R.T. Tiekink, R. Karvembu, Inorg. Chim. Acta 404
(2013) 82-87.
[24] A.F. Elhusseiny, A. Eldissouky, A.M. Al-Hamza, H.H.A.M. Hassan, J. Mol. Struct. 1100 (2015)
530-545.
[25] N. Selvakumaran, S.W. Ng, E.R.T. Tiekink, R. Karvembu, Inorg. Chim. Acta 376 (2011) 278-284.

[26] R.S. Correa, K.M.D. Oliveira, F. G. Delolo, A. Alvarez, R. Mocelo, A.M. Plutin, M.R. Cominetti, E.E.
ACCEPTED MANUSCRIPT
Castellano, A.A. Batista, J. Inorg. Biochem. 150 (2015) 63-71.
[27] M.G. Woldu, J. Dillen. Theor. Chem. Acc. 121(1) (2008) 71-82.
[28] A. Saeed, M. Bolte, M.F. Erben, H. Pérez, CrystEngComm 17 (2015) 7551-7563.
[29] R.R. Cairo, A.M.P. Stevens, T.D.D. de Oliveira, A.A. Batista, E.E. Castellano, J. Duque, D.B. Soria,
A.C. Fantoni, R.S.Corrêa, M.F. Erben, Spectrochim. Acta A 176 (2017) 8-17.
[30] A. Saeed, M.F. Erben, N. Abbas, U. Flörke, J. Mol. Struct. 984 (2010) 240-245.
[31] A. Saeed, M.F. Erben, M. Bolte, J. Mol. Struct. 985 (2011) 57-62.
[32] A. Saeed, M.F. Erben, U. Shaheen, U. Flörke, J. Mol. Struct. 1000 (2011) 49-57.
[33] A. Saeed, M.F. Erben, M. Bolte, Spectrochim. Acta A 102 (2013) 408-413.
[34] A. Saeed, S. Ashraf, J.M. White, D.B. Soria, C.A. Franca, M.F. Erben, Spectrochim. Acta A 150 (2015)
409-418.
[35] H.M. Abosadiya, E.H. Anouar, S.A. Hasbullah, B.M. Yamin, Spectrochim. Acta A 144 (2015) 115-124.
[36] V. Arjunan, R. Anitha, G. Durgadevi, M.K. Marchewka, S. Mohan, J. Mol. Struct. 1133 (2017) 187-198.
[37] D.M. Gil, M.D. Lestard, O. Estévez-Hernández, J. Duque, E. Reguera, Spectrochim. Acta A 145 (2015)
553-562.
[38] M.E.D. Lestard, D.M. Gil, O.E. Hernández, J. Duque, M.F. Erben, J. Duque, New J. Chem. 39 (2015)
7459-7471.
[39] A. Saeed, A. Khurshid, M. Bolte, A.C. Fantoni, M.F. Erben, Spectrochim. Acta A 143 (2015) 59-66.
[40] A. Saeed, A. Khurshid, J.P. Jasinski, C.G. Pozzi, A.C. Fantoni, M.F. Erben, Chem. Phys. 431-432 (2014)
39-46.
[41] H.M. Abosadiya, S.A. Hasbullah, B.M. Yamin, Chinese J. Struct. Chem. 34 (2015) 379-385.
[42] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery,
Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci,
M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R.
Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E.
Knox, H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J.

Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, A. Voth, P. Salvador, J.J.
ACCEPTED MANUSCRIPT
Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D.
Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski,
B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A.
AleLaham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W.
Wong, C. Gonzalez, J.A. Pople, Gaussian Inc., Wallingford, CT, 2009.
[43] M.J. Frisch, J.A. Pople, J.S. Binkley, J. Chem. Phys. 80 (1984) 3265ꢄ3269.
[44] G.M. Sheldrick, Acta Crystallogr. A64 (2008) 112ꢄ122.
[45] G.M. Sheldrick, Acta Crystallogr. C 71 (2015) 3-8.
[46] K. Brandenburg, Diamond, 102, 53227 Bonn, Germany (2006).
[47] A.L. Spek, Acta Crystallogr. D 65 (2009) 148-155.
[48] C.F. Macrae, I.J. Bruno, J.A. Chisholm, P.R. Edgington, P. McCabe, E. Pidcock, L. Rodriguez-Monge,
R. Taylor, J. van de Streek, P.A. Wood, J. Appl. Cryst. 41 (2008) 466-470.
[49] J.J. McKinnon, D. Jayatilaka, M.A. Spackman, Chem.Commun. 2007, 3814-3816.
[50] M.A. Spackman, D. Jayatilaka, CrystEngComm 11 (2009) 19-32.
[51] M.A. Spackman, Phys. Scr. 87 (2013) 048103.
[52] J.J. McKinnon, M.A. Spackman, A.S. Mitchell, Acta Crystallogr. Sect. B: Struct. Sci. 60 (2004)
627-668.
[53] S.K. Wolff, D.J. Grimwood, J.J. McKinnon, M.J. Turner, D. Jayatilaka, M.A. Spackman,
CrystalExplorer (Version 3.1), University of Western Australia, 2012.
[54] S.K. Seth, D. Sarkar, A. Roy and T. Kar, CrystEngComm, 13 (2011) 6728-6741.
[55] S.K. Seth, Inorg. Chem. Commun. 43 (2014) 60-63.
[56] P. Manna, S.K. Seth, A. Das, J. Hemming, R. Prendergast, M. Helliwell, S. R. Choudhury, A. Frontera
and S. Mukhopadhyay, Inorg. Chem. 51 (2012) 3557-3571.
[57] A. Saeed, S. Ashraf, U. Flörke, Z.Y.D. Espinoza, M.F. Erben, H. Pérez, J. Mol. Struct. 1111 (2016)
76-83.
[58] M.A. Spackman, D. Jayatilaka, CrystEngComm. 11 (2009) 19-32.

[59] I.B. Douglas, F. B. Dains, J. Am. Chem. Soc. 56 (1934) 719-721.
ACCEPTED MANUSCRIPT
[60] M.K. Rauf, A. Badshah, U. Flörke, Acta Crystallogr. E 62 (2006) o2452-o2453.
[61] M.K. Rauf, A. Badshah, U. Flörke, Acta Crystallogr. E 62 (2006) o3823-o3825.
[62] M.K. Rauf, A. Badshah, M. Bolte, Acta Crystallogr. E 62 (2006) o4299-o4301.
[63] L. Qiao, J. Huang, W. Hu, Y. Zhang, J. Guo, W. Cao, K. Miao, B. Qin, J. Song, 1139 (2017) 149-159.
[64] B.M. Yamin, M.S.M. Yusof. Acta Crystallogr. E 59 (2003) o151–o152.
[65] J. Bernstein, R.E. Davis, L. Shimoni, N. Chang, Angew. Chem. Int. Ed. Engl. 34 (1995) 1555-1573.
[66] C. Jelsch, K. Ejsmont, L. Huder, IUCrJ 1 (2014) 119-128.
[67] A. Saeed, Z. Ashraf, M.F. Erben, J. Simpson, J. Mol. Struct. 1129 (2017) 283-291.
[68] C.G. Overberger, H.A. Friedman, J. Polym. Sci. A 3 (1965) 3625-3634.

Highlights
：
ACCEPTED MANUSCRIPT
1. The three isomeric acyl thiourea compounds were firstly prepared and characterized.
2. Intermolecular contacts were explored using both the Hirshfeld surfaces and their 2D fingerprint plots.
3. Conformational aspects are discussed in terms of the X-ray diffraction analysis and the vibrational
spectra.
4. The computed vibrational spectra are in good agreement with the experimental results.