Synthesis, Crystal Structure and Theoretical Calculation Studies on 1-(4-chloromethyl-benzoyl)-3-(mono-substituted) thioureas①

ZHANGYu HU Wei QIAO Lei ZHANG Xing SONG Ji-Rong, HUANG Jie

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Synthesis, Crystal Structure and Theoretical Calculation Studies on 1-(4-chloromethyl-benzoyl)-3-(mono-substituted) thioureas①

ZHANGYuaHU WeibQIAO LeiaZHANG XingaSONG Ji-Ronga,cHUANG Jiea②

a(/710069)b(710000)c(100009)

crystal structure, Hirshfeld surfaces, UV-vis, ESP;

1 INTRODUCTION

Usually, 1-acyl/aroyl thioureas (RCONHCSNR1R2) with the properties of stable structures and good biological activity were proverbially synthesized to apply to a variety of fields, for instance, as ligands to prepare new materials[1, 2], herbicides[3]in the area of agriculture, and organocatalysts[4, 5], as well as bio-logical activity of antiviral[6]and antimicrobial[7]. Due to the existence of O, S and N donor atoms in the central thiourea group moiety, it often facilitates to form complexes with various transition me- tals[8-10]. At the same time, it was also used to study pharmacological activity through molecular docking methods by our research group[11].

From the point of view of synthetic ways, phase transfer catalysis, which is often adopted by people using PEG-400 reagent[12, 13], is a very attractive route. The reaction time is at least 6～7 hours. However, Zhang et al.[14]had demonstrated that ultrasonic radiated method can significantly shorten the reaction time and improve the yield through the experimental comparison. This method can also reduce the use of solvents to make post-processing easier, in line with green chemical requirements. Therefore, the combination of the two methods to prepare thiourea derivatives is a promising approach.

In addition, the structural characteristics of thiourea molecules had increasingly become the focus of many experts’ researches in recent years. According to previous reports, 1-acyl/aroyl thioureas displayed mono- (RCONHCSNHR1) and di-substi- tuted (RCONHCSNR1R2), un-(RCONHCSNH2) in the 3-position N atom, resulting in thiourea molecules which showed common S and U-shaped conformations in previous studies[15-20], respectively. Besides, when the thiourea derivatives as an intermediate were synthesized heterocyclic com- pounds[21-23], the reaction sites are sections that we must consider. Thence, the investigation of molecu- lar electrostatic potential is particularly important. Electrostatic potential (ESP) is an exceedingly essen- tial tool to both predict chemical active sites[24, 25]and explore molecular recognition[26]and intermo- lecular interaction[27, 28]. As we all know, the theore- tical basis is that molecules tend to approach with each other in a complementary way of ESP[28]. Specifically, through analyzing the magnitude and position of the minima and maxima on the vdW surface, the intensity and orientation of many non-covalent interactions, such as hydrogen bonding, halogen bonding and-hole bonding can be also well predicted and interpreted by Politzer et al.[29-32]. Compared with the previous electrostatic potential analysis[33, 34], ESP surface with extrema can be more intuitively, and clearly show the active site of the thiourea molecules by Multiwfn software[35], which has never been reported in the thioureas field before.

We investigated the 1-aroyl-3-(mono-substituted) thioureas in this article. Unlike before, 1-(4-chloro- methylbenzoyl)-3-(4-nitrophenyl) thiourea (1) and 1-(4-chloromethylbenzoyl)-3- (benzothiazole-2-yl) thiourea (2) had been synthesized with phase trans- fer catalysis combined with ultrasonic radiation method and been characterized. Quantum chemical calculations were performed as a support to verify with the experimental data each other. So, we used density functional theory (DFT) to calculate the vibrational spectra (IR) for compounds 1 and 2, HOMO-LUMO orbitals and UV-Vis absorption. The electrostatic potential (ESP) associated with the electron density was calculated. Finally, the Hirshfeld surfaces were applied to explain the short contacts between the molecules and the relative contribution of different contacts for the entire molecular surface was given directly by the 2fingerprint plots.

2 EXPERIMENTAL

2. 1 Measurements and instruments

All the chemicals utilized in this work were commercially available from Sigma Aldrich (St Louis, MO, USA). Ultrasound irradiation synthesis was carried out using a PS-100A ultrasonic cleaning machine with the appropriate power settings. Melting points were recorded using a Cossim KER3100-08S apparatus and are uncorrected. The FT-IR (KBr pellets) spectra were recorded in the 400～4000 cm-1range using a Bruker EQUINOX 55 FT-IR spectrometer.1H nuclear magnetic resonance (NMR) spectra were determined in dimethylsul- foxide-d6at 400 MHz using a Bruker spectrophoto- meter. Mass spectra were recorded on a MAT-112-S spectrometer at 70 eV. The UV-Vis spectra were measured in the 100～900 nm range with methanol as solvent using a SHIMADZU UV-3600 spectro- photometer. Elemental analyses were on an ELEMENTAR Vario EL Ⅲ elemental analyzer.

2. 2 Synthesis of aroyl thiourea

A solution of an appropriate 4-chloromethylbenzoyl chloride (1.44 mL, 10 mmol) in ethyl acetate (50 mL) was added dropwise to a three-necked round-bot- tomed flask containing KSCN (1.457 g, 15 mmol) and seven drops of PEG-400. The mixture was transferred to an ultrasonic cleaner with a power of 600 W at 60 ℃. After 50 min, the 4-nitroaniline (1.31g, 9.5 mmol) or 1-aminobenzothiazole (1.42 g, 9.5 mmol) was added and the ultrasound was continued for 30 min. After the reaction was completed, the mixture in the flask was poured into a beaker containing 600 mL of cold water and filtered. Then the crude product was purified by recrystallization from the dichloromethane:methanol mixture (Scheme 1).

2. 2. 1 1-(4-Chloromethylbenzoyl)- 3-(4-nitrophenyl) thiourea (1)

The title compound was obtained aslight yellow powder. Yield: 3.12 g, 92%. m.p. 172.8～173.2 ℃. Anal. Calcd. for C15H12ClN3O3S: C, 51.60, H, 3.44, N, 15.04%. Found: C, 51.23, H, 3.85, N, 15.28%. FT-IR:,cm-13335 (w, N–H stretching), 2989 (m, aromatic C–H stretching), 2899 (m, chloromethyl C–H stretching), 1666 (m, C=O stretching), 1517 (s, aromatic C=C stretching), 1314, 1148, 1109 (vs, C–N stretching), 747 (s, C=S stretching), 671 (m, C–Cl stretching).1H NMR (400 MHz, DMSO-6):, ppm 4.86 (2H, s, CH2Cl), 7.60 (2H, d,= 8.0 Hz, CAr–H), 8.00 (2H, d,= 8.0 Hz, CAr–H), 8.08 (2H, d,= 8.0 Hz, CAr–H), 8.29 (2H, d,= 8.0 Hz, CAr–H), 11.80 (1H, s, NH), 12.82 (1H, s, NH). MS (EI)/(70 eV): 350.82 [M]+.

2. 2. 2 1-(4-Chloromethylbenzoyl)-3- (benzothiazole-2-yl) thiourea (2)

The title compound was obtained as yellow powder. Yield: 2.87 g, 84%. m.p. 191.3～192.5 ℃. Anal. Calcd. for C16H12ClN3OS2·CH3OH: C, 53.11; H, 3.32; N, 11.62%. Found: C, 53.52; H, 3.85; N, 11.41%. FT-IR:, cm-13315 (w, N–H stretching), 2988, 2901 (s, aliphatic C–H), 1666 (m, C=O stretching), 1529 (s, aromatic C=C stretching), 1066 (vs, methanol C–O stretching), 791 (m, C=S stretching), 647 (m, C–Cl stretching).1H NMR (400 MHz, DMSO-d6):, ppm 4.86 (2H, s, CH2Cl), 7.40 (1H, m), 7.51 (1H, m), 7.62 (2H, t,= 8.0 Hz), 7.81 (1H, t,= 8.0 Hz), 8.04 (3H, q,= 8.4 Hz, CAr–H), 12.30 (1H, s, NH), 14.25 (1H, s, NH). MS (EI)/(70 eV): 394.87 [M]+.

Scheme 1. Synthetic route of thiourea compounds 1 and 2

2. 3 Crystal data and structure determination

The yellow crystal of 1 (0.31mm× 0.26mm × 0.13mm) was selected for X-ray diffraction analysis. Data collection was performed on a Bruker SMART APEX CCD diffractometer[36]equipped with a graphite-monochromatic Mo-radiation (= 0.71073 ?) by using a-scan mode at 296(2) K. A total of 7492 reflections were collected in the range of 1.57<<25.10o, of which 2731 were independent withint= 0.0674. The solution and refinement of the structures were solved by direct methods with SHELXS 97[37]. The non-hydrogen atoms were refined by full-matrix-block least-squares method on2with anisotropic thermal parameters by means of SHELXS-97[38]. Molecular structures were genera- ted by the MERCURY program[39], and packing diagrams were depicted using Diamond program and additional metrical data were calculated using PLATON[40]. Hydrogen atoms were positioned geometrically and constrained with riding model position parameters and fixed isotropic thermal parameters. The final refinement gave= 0.1130 and= 0.3621 (= 1/[2(F2) + (0.3000)2+ 0.3038], where= (F2+ 2F2)/3),= 1.032, (Δ/)max= 0.000, (Δ/)max= 0.9114 and (Δ/)min= –0.8158 e/?3. The yellow crystal of 2 (0.33mm× 0.27mm × 0.14mm) was selected for X-ray diffrac- tion analysis. Data collection was performed on a Bruker SMART APEX CCD diffractometer equip- ped with a graphite-monochromatic Mo-radia- tion (= 0.71073 ?) by using a-scan mode at 296(2) K. A total of 4906 reflections were collected in the range of 1.52<<26.28o, of which 3536 were independent withint= 0.0265. The solution and refinement of the structures were solved by direct methods with SHELXS-97. The non-hydrogen atoms were refined by full-matrix-block least- squares method on2with anisotropic thermal para- meters by means of SHELXS-97. Molecular struc- tures were generated by the MERCURY program, and packing diagrams were depicted using Diamond program and additional metrical data were calculated using PLATON. Hydrogen atoms were positioned geometrically and constrained with riding model position parameters and fixed isotropic thermal parameters. The final refinement gave= 0.0657 and= 0.1812 (= 1/[2(F2) + (0.1256)2], where= (F2+ 2F2)/3),= 1.030, (Δ/)max= 0.000, (Δ/)max= 0.5551 and (Δ/)min= –0.4703 e/?3.

2. 4 Theoretical calculation

The X-ray structures of compounds were severed as the initial geometry and fully optimized by using B3LYP/6-311+G (d,p) levels through the Gaussian 09 program[41](Fig. S4). And we further calculated the vibration frequency for the stable structures to obtain the infrared and HOMO-LUMO orbitals in gas phase. The interactions between different elec- tron transitions within the molecules were computed to illustrate causing the stability of molecules and the excited states of the UV-Vis absorption by TD-DFT method in the case where the solvent was considered. ESP surfaces (red-white-blue) were performed as a quantitative analysis of molecular surface and then expressed by a molecular graphics program VMD 1.9.3[42]. Finally, we used the CrystalExplorer 3.1 package[43]to calculate the Hirshfeld surfaces of the molecules and analyzed the short contacts between the molecules. The relative contribution of different contacts to the entire molecular surface was given directly by the 2fingerprint plots.

3 RESULTS AND DISCUSSION

3. 1 Spectroscopic data

3. 1. 11H NMR analysis

The1H NMR of the two structures are shown in Figs. S1 and S2 in the Supplementary information. The formation of intramolecular hydrogen bonds causes the chemical shifts of the protons to move to the downfield[44]. Thus, the chemical shift of the proton of the thioamide in structure 1 was greater than the free proton in the amide, assigning at 12.82 and 11.80 ppm, respectively. While the chemical shifts of the thioamide and amide protons for structure 2 were significantly larger as compared with 1 appearing at 14.25 and 12.30 ppm, respec- tively, owing to the hydrogen bonds between the imino N–H and the oxygen atoms of the carbonyl group, methanol solvent. The aromatic protons of structure 1 were placed in the range of 7.59～8.30 ppm, where the shifts of the two protons adjacent to the nitro group were the greatest at 8.29 ppm, as a result of deshielded effect of the nitro group. The methylene protons of the two compounds conform with the shift in 4.86 ppm.

3. 1. 2 Infrared spectra analysis

We measured the infrared spectrum in the solid state and compared with the calculation in the gas phase regardless of the vibrational wavenumber or absorption intensity, and the significant differences between the two can be found (see Fig. S3 in Supplementary information).

For thiourea molecules, it was liable to observe the harmonic frequency of the central -C=O–NH–C=S–NH- moiety. The characteristic absorption peak of aromatic ketone was normal in 1680～1700 cm-1, which is attributed to the carbonyl stretching vibration. The experimental results showed that the carbonyl C=O stretching models of compounds 1 and 2 are distributed at the same value 1666 cm-1, and the corresponding calculated values were absorbed at 1720 and 1715 cm-1, respectively. Since the carbonyl groups of both compounds formed intramolecular hydrogen bonds with the H atoms of phenyl and thioamide respectively, the frequency of the stretching vibration was reduced. The stretching vibration frequency of C=S was respectively assigned at the measured values 747, 791 cm-1and calculated values 766, 797 cm-1for 1 and 2. The strongest absorption peaks at 1314, 1148, 1109 cm-1(Exp.) and 1347, 1170, 1120 cm-1(Calcd.) in infrared spectrum were considered as the stre- tching vibrations of C–N single bonds in compound 1, 1313, 1157 cm-1(Exp.) and 1350, 1197 cm-1(Calc.) in 2. While the experimental stretching vibrations of N–H of 1 appeared as a medium band at 3335 cm-1in the FT-IR spectra, and the corres- ponding calculated value appeared at 3316 cm-1.

According to previous reports, the C=C bonds on aromatic ring stretching models fall in the range of 1430～1640 cm-1[45]. The characteristic peaks of the carbon-carbon double bonds were observed at 1517 and 1529 cm-1for compounds 1 and 2, respectively. In addition, the stretching vibrations of C–H on the aromatic rings appeared only in the simulated infrared spectrum of 2, and here was a weak absorption at 3072 cm-1. The C–H groups of methyl and methylene of molecule 2 were broadly absorbed at 2988 and 2901 cm-1, respectively.

The C–Cl stretching vibrations on the chlorome- thyl group were measured at 671 cm-1(1) and 647 cm-1(2) respectively. The N–O vibration of the nitro group in 1 appeared as a moderate intensity peak at 1261 cm-1which was obtained by experiments. Furthermore, the C=N double bond stretching vibra- tion wavenumbers on the fused ring of compound 2 were found at 1503 cm-1(Exp.) and 1509 cm-1(Calcd.). The calculated and experimental charac- teristic peaks were attributed to O–H stretching vibration at 3838 and 3665 cm-1, respectively.

3. 1. 3 UV-visible spectra analysis

Combining the frontier orbitals (HOMO-LUMO) with the electronic absorption spectra can well reflect the nature of the electronic transitions in the molecules[46-48]. And we calculated the UV-vis spectra of both compounds using the TD-DFT method for gas phase and methanol as solvent (Fig. 1). The results showed that the experimental and theoretical values have a greater consistency. The selected plots of the frontier molecular orbitals together with their energy (unit: eV) are shown in Fig. 2.

Both compounds 1 and 2 had maximum absorp- tion peaks at the experimental values= 281 nm, while the theoretical values were 310.5 and 290 nm in the tested compounds, respectively because the conjugation effect in the system makes the absorp- tion redshift. Additionally, we also calculated the relative contribution values of the electronic transi- tions in different orbitals, excited energies and oscillator strengthsat the corresponding absorption wavelengths, as listed in Table 1. The absorption at 373.5 nm had the largestvalue than others in compound 1, and was assigned to the transition from HOMO–1 to LUMO orbital (contribution: 98.9%) exhibiting the nature of→*. There were in compound 2 a greater number of electronic transitions distribution relative to compound 1, especially the absorption at 235.4 nm with the smallestto be 0.0455 in connection with HOMO–5 → LUMO+1 (31%), HOMO–4 → LUMO+1 (28.5%), HOMO–4 → LUMO+2 (8.2%), HOMO–1 → LUMO+2 (8%) and HOMO → LUMO+4 (5.8%) transitions. Finally, since the HOMO orbitals were mainly distributed in the thiourea groups moiety for compound 1 and the fused ring hydrocarbyl and the atom of sulfur of thiourea moiety for compound 2, the composition of LUMO was throughout the whole two molecules. Thus the transitions from HOMO to LUMO molecular orbitals revealed an essence of→* in 1 and 2.

Fig. 1. Calculated and experimental UV-visible spectra of compounds 1 (a) and 2 (b) in methanol

Fig. 2. Frontier orbital plots of the thiourea compounds

Table 1. Calculated Absorption Wavelength (nm) and Oscillator Strengths of the Most Significant Excited States for 1 and 2

3. 2 Crystal structure analysis

The selected crystal refinement parameters were listed in Table 2. It can be seen from Fig. 3 that the positions of the C=O and C=S double bonds relative to the N–H bond show an S-shape in the target compounds. Table S1 in Supplementary information displayed selected dihedral angle parameters of structures 1 and 2. In general, the isolated C–N single bond and C=N double bond lengths are 1.48 and 1.32 ?, respectively. The bond lengths of N(1)–C(8), N(1)–C(9) and N(2)–C(9) of structure 1 are 1.381, 1.415 and 1.344 ?, respectively, illustra- ting a conjugation among the N(2), C(9), N(1), C(8) atoms. The S(1)–C(9) bond length demonstrated the double bond distance characteristic for structure1, since S(1) as an acceptor atom formed an intra- molecular hydrogen bond (C–H···S=C) with H(15) atom on the benzene ring B (Table 3). While in 2, the O(2) atom of the methanol molecule as an acceptor formed intermolecular hydrogen bonds (C–H···O=C, N–H···O=C) of N(1)–H(1) and C(4)–H(4) of the thiourea molecule, respectively, so that the O(2)–C(17) bond length was lower than normal (1.361 ? < 1.425 ?).

The bond angle C(9)–N(2)–C(10) of 129.7° was much larger than C(10)–S(2)–C(16) (87.7°) on the thiazole ring of structure 2, for the nitrogen atom as a central atom with higher electronegativity is relative to the sulfur atom which is in good agreement with the previous report[49], and showed an2hybridization on the N(8) atom. As can be seen from Table S1, the torsion angles C(1)–C(2)–C(3)–C(4) and C(3)–C(4)–C(5)–C(8) are 179.1°, 177.2° for 1 and 179.3°, 177.8° for 2, respectively, indicating that atoms C(1) and C(8) are coplanar with the benzene ring.

Two types of hydrogen bonds (intra-, inter-) of the two compounds were listed in Table 3. And it is not difficult to find the distance of the hydrogen bond (H···S) formed by sulfur as the acceptor atom and hydrogen atom was longer than the others. The molecular packing diagram (Fig. 4) showed the centro-symmetric three-dimensional network struc- ture for 1 formed a seven-membered closed loop by intermolecular hydrogen bonds N(1)–H(1)···O(3) (1–, 0.5+, 0.5–), C(4)–H(4)···O(3) (1–, 0.5+, 0.5–) and C(6)–H(6)···O(2) (1–, 1–, –). The intermolecular hydrogen bond C(6)–H(6)···O(1) (–, 1–, –) led to chain dimers in 2 along thedirection. The two molecules were stabilized through···stacking and van der Waals forces to form complex accumulation space structures. It is noteworthy that the two oxygen atoms of the nitro group as the acceptor sites make it meaningful for structure 1 to form an extended hydrogen bond network.

Fig. 3. Crystal structures of both compounds 1 and 2 at 50% probability displacement ellipsoids. The dashed lines indicate the hydrogen bond within the molecule. The two benzene rings in structure 1 are distinguished by A and B symbols

Table 2. Selected Bond Lengths (?) and Bond Angles (°) for Compounds 1 and 2

Table 3. Hydrogen Bonding Geometrical Parameters of Compounds

Symmetry codes: (a) 1–, 0.5+, 0.5–; (b) 1–, 0.5+, 0.5–; (c) 1–, 1–, –; (d) –, 1–, –

Fig. 4. Crystal packing diagrams of compounds 1 and 2 viewed down theaxis. The dashed lines denote the intermolecular hydrogen bonds

3. 3 Electrostatic potential analysis

The ESP graphics with surface extrema of both compounds are shown in Fig. 5, and the quantitative distribution of the electrostatic potential of the molecular surfaces was represented by a bar graph in Fig. 6.

The uneven distribution of electron density led to positive and negative electrostatic potentials on the molecular vdW surface. The negative regions of ESP (red color) were related to possible electrophilic reaction sites, while the positive regions (blue color) to the nucleophilic reactivity. From Fig. 5 over all views, the most negative value –36.12 kal·mol-1on the vdW surface appeared on the nitro group as the global surface minimum of compound 1. That is a susceptible site for electrophilic attack, and also makes O(3) atom readily form intermolecular hydro- gen bonds (N(1)–H(1)···O(3), C(4)–H(4)···O(3)). The most positive electrostatic potential was on the amide and hydroxyl groups in molecules 1 and 2, 46.16 and 54.41 kal·mol-1, respectively, representing a feasible site for nucleophilic attack. Simulta- neously, it was not difficult to find that each negative potential region is on electronegativity atoms (O, S, N) and each positive potential region is around the hydrogen atoms.

Fig. 6 reflected the fact that the vdW surface area for compound 2 is 154.6 ?2, which accounts for 37.5% of the total surface, while for compound 1 only 20.3% in the ESP values of –25 to –5 kal·mol-1range. In the zero potential region (white color), the surface areas of the two compounds were approxi- mately equal. Therein, the increase of electron delocalization on the benzene ring B in 1 led to zero potential for the polarity of the nitro group.

Fig. 5. Electrostatic potential (ESP) plots mapped on the vdW surface of compounds 1 and 2. The cyan and purple spheres represent local minima and maxima of ESP surface, respectively, and the extrema of back of the picture are shown as light spheres. The total electrostatic potential maximum and minimum are indicated by. In addition, some meaningless values such as negative values in the maximum points and positive values in the minimum points are discarded

Fig. 6. Surface area corresponds to different electrostatic potential values of both compounds 1 and 2

3. 4 Hirshfeld surface analysis

Hirshfeld surfaces and 2fingerprint plots were exploited for the analysis of intermolecular interac- tions[50]. Thereinto, Hirshfled surfaces were a molecule with its nearest molecules in contact with the weight function of 0.5, includinge,i,normand various functions of distance[51], and the normalized contact distancenormwas defined by M. A. Spackman in terms ofe,iand the vdW radii of the atoms to highlight close contact when a molecule contains large atoms (like Br or I)[52]. Thus we displayed the mapped withnormsurfaces of the thiourea compounds in Fig. 7. Furthermore, the relative contributions and (e+i) values of different short contacts[53, 54]such as O···H/H···O, C···H/H···C, H···H, S···H/H···S, Cl···H/H···Cl contacts to intermolecular interactions can be distinctly presented in the two-dimensional fingerprint plots (Figs. 8 and 9).

From the view ofnormsurfaces for compound 1, the intermolecular O···H, labeled 2, and S···H (labeled 1) reciprocal contacts with bigger red regions relative to the Cl···H (labeled 3) contacts represented stronger interactions, and the vast majority of distances shorter than sum of vdW radii were O···H contacts. It is precisely because of the R1 2(7)ring formed through these strong intermolecular hydrogen bonds (C(4)–H(4)···O(3) and N(1)–H(1)···O(3), Table 2), as shown in Fig. 3. While the S···H intermolecular interaction with light red color illustrated that its contacts are longer than O···H, and the existence of weaker Cl···H interactions is an indispensable factor stabilizing the molecules. Compared to 1, there were less intermolecular con- tacts (red spots) in compound 2, and some of the contacts were relatively weaker, just like the S···H (labeled 1) and H···H (labeled 3) contacts. Similarly, thenormsurfaces for 2 with more red spots (labeled 2) were related to C(6)–H(6)···O(1) hydrogen bonds forming R2 2(10)graph-set motifs. Besides, the intermolecular contacts between the benzene ring B and the fused ring moiety were not much different, respectively in compounds 1 and 2.

A pair of short spikes ate+i～ 1.55 ? in compound 1 is related to S···H, attributing to interactions between S(1) atom on the thiocarbonyl and H(7) atom on the benzene ring A. The contribution (8.4%) of the C–H···S contacts to the entire surface was less relative to the C–H···Cl (14.2%). Thee+ivalues of Cl···H contacts of compounds 1 and 2 were about 2.90 and 2.96 ?, respectively. For compound 2, the contribution of S···H contacts was 14.3% because the fused ring moiety containing S atom enhanced the contribution of S···H interactions to the entire molecular surface. As well, the contribution of O···H intermolecular interactions in compound 1 (21.5 %) was more than that of 2 (6.2%). For there were aromatic rings in both molecules, the difference of the contribution of C–H···C interactions is not great. Two pairs of spikes ate+i～2.4 ? in the fingerprint plots belonging to the conventional H···H contacts contributed the most to the entire Hirshfeld surfaces, on account of interatomic interactions between H(6) of the benzene ring A and H(12) of the benzene ring B of 1, and between H(1A) of the chloromethyl and H(12) of the fused ring in 2. The 6.0% and 6.1% values of C···C contacts were due to the···stacking interactions in the molecules. The other contacts with low contribution to the Hirshfeld surfaces may not have an impact on the molecular packing.

Fig. 7. Hirshfeld surfaces of compounds 1 and 2 from the view of two orientations. The red spots indicated that the intermolecular contacts are shorter than the sum of vdW radii

Fig. 8. 2fingerprint plots of compound 1 and the relative contribution for different contacts

Fig. 9. 2fingerprint plots of compound 2 and the relative contribution for different contacts

4 CONCLUSION

1-Aroyl mono-substituted thiourea derivatives have been synthesized and characterized. The vibrational and electronic properties of the thiourea molecules are determined by combining the experimental and theoretical calculations, and the results reveal them in good agreement. The struc- tural and conformational properties of compounds 1 and 2 were determined by X-ray single-crystal diffraction. The Hirshfeld surfaces and 2finger- print plots were carried out to clearly explain the intermolecular interactions and their quantitative contributions to the crystal packing of the two thiourea compounds. In addition, the chemical activity sites of the title compounds were also evaluated by the ESP.

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12 August 2017;

20 November 2017 (CCDC1439446 for1 and1465494 for 2)

① This project was supported by the Science and Technology Program of Shaanxi Province(No.2013K02-25), the Science and Technology Program of Xi’an(No. NC1404) and the Science and Technology Research and Development Program of Shaanxi Province(No.14JF025)

. Huang Jie. female, born in 1969, professor, doctor of engineering, majoring in the synthesis of organic compounds with biological activities and doing researches on crystal structure and theoretical calculation. Tel: +86 029 88307755. E-mail: huangjie@nwu.edu.cn

10.14102/j.cnki.0254-5861.2011-1806