Synthesis and Characterization of N-(Arylcarbamothioyl)-cyclohexanecarboxamide Derivatives: The Crystal Structure of N-(Naphthalen-1-ylcarbamothioyl)cyclohexanecarboxamide

A number of N-(arylcarbamothioyl)cyclohexanecarboxamide derivatives (aryl substituents: phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, o-tolyl, p-tolyl, 3-methoxyphenyl, 4-methoxyphenyl and naphthalen-1yl) have been synthesized. The compounds obtained were characterized by elemental analyses, IR spectroscopy and 1H-NMR spectroscopy. N-(naphthalen-1-ylcarbamothioyl)cyclohexanecarboxamide, H2L9, was also characterized by a single crystal X-ray diffraction study. This compound, C18H20N2OS, crystallizes in the triclinic space group Pī, with Z = 2, and unit cell parameters a = 6.9921(14) Å, b = 11.002(2) Å, c = 12.381(3) Å, α = 113.28(3)°, β = 99.38(3)°, and γ = 101.85(3)°. The cyclohexane ring adopts a chair conformation. The molecular conformation of the compound is stabilized by an intramolecular (N2-H2•••O1) hydrogen bond which forms a pseudo-six-membered ring.


Introduction
Chelating extractants have been found to be more selective for separating metal ions than solvating reagents and anion exchangers. Some of the most important chelating extractants are thiourea derivatives, which have been known for a long time and are easily synthesized in good yields. Metal complexes of thiourea derivatives have been the subject of considerable study [1][2][3][4][5][6][7][8][9][10][11][12][13]. The presence of hard O-and N-and soft S-donor atoms in the backbones of these ligands enable them to react readily with both transition group and main group metal ions, yielding stable metal complexes, some of which have been shown to exhibit interesting physico-chemical properties and significant biological activities [13][14][15]. They have received particular attention because of their potential use as highly selective reagents for the pre-concentration and separation of metals [16][17][18][19][20]. Some thiourea derivatives have been found to be useful as insecticides, fungicides, herbicides, and plant-growth regulators [13,14,21,22]. In recent years, thiourea derivatives have been the subject of interest because it has been shown that they have antitumor and antifungal bioactivities and inhibitory activities against viruses [15,23,24].
Over the past couple of years we have been focusing on the preparation and characterization of new carboxamides which are bonded with a thiourea group [1][2][3][4][5][25][26][27][28][29][30][31][32]. Taking into consideration all the features described above, we focused our efforts in the present work on the synthesis of carboxamide derivatives. We have now obtained nine novel carboxamide derivatives and, in this paper, we report the preparation and characterization of these new derivatives: , N-(4-methoxyphenylcarbamothioyl)cyclohexanecarboxamide (H 2 L 8 ) and N-(naphthalen-1-ylcarbamothioyl)cyclohexanecarboxamide (H 2 L 9 ). The crystal structure of the last compound is also described.

Results and Discussion
The synthesis of intermediate and target compounds were performed as illustrated in Figure 1. The derivatives were synthesized in excellent yields following the method described by Douglass and Dains [33], which involved the reaction of a cyclohexanecarbonyl chloride with potassium thiocyanate in acetone followed by condensation of the resulting cyclohexanecarbonyl isothiocyanate with the appropriate primary amine. All spectroscopic methods and elemental analyses confirm the proposed structures of the new compounds.
The characteristic IR bands of the synthesized compounds are presented in the Experimental section. The compounds showed two peaks in the 3256-3227 cm -1 and 3215-3134 cm -1 regions due to the N-H stretching vibrations. This difference between the ν NH stretching vibration frequencies is due to an intramolecular hydrogen bond (X-ray single crystal diffraction data), whereby the carbonyl group is connected to the imine group. Compounds showed a single peak in the 1690-1682 cm -1 region, which was due to the C=O stretching vibration. A strong band in the 1252-1238 cm -1 region is assigned as the thiocarbonyl group stretching vibration band. These results agree with the literature data [1][2][3][4][5]25,26,[33][34][35].  The 1 H-NMR data of the compounds are presented in the Experimental section. The 1 H-NMR spectra of the compounds are consistent with the structural results. We discuss only the N-H signal of the investigated compounds. The two N-H signals for the compounds are observed in the 12.15-12.62 ppm region and in the 8.76-9.21 ppm range. Because of the formation of an intramolecular hydrogen bond, the imine group proton participating in the hydrogen bond appears at low field [34]. The other imine proton appears at high field. This data agrees with the results of Li et al. and Mansuroglu et al. [26,35]. All of these data agree with FT-IR ATR and X-ray single crystal diffraction results.
Absorption coefficient (mm -1 ) 0.200 F(000) 332 Crystal size (mm 3 ) 0.29 x 0.24 x 0.14 θ range for data collection (°) 3.37 to 25.05 Index ranges   The conformation of the H 2 L 9 molecule with respect to the thiocarbonyl and carbonyl moieties is twisted, as reflected by the torsion angles O1-C12-N1-C11, C12-N1-C11-N2, and S1-C11-N1-C12 of -1.23 o , 6.42 o and 176.83 o , respectively. The O1-C12-N1-C11-N2 plane has a maximum deviation of 0.038(4) Å for C11 atom. However, the central carbonyl thiourea moiety (S1-C11-N2-N1-C12-O1) connecting the naphthalene and cyclohexane groups is almost planar, with the O1 atom deviating by 0.047(4) Å. In addition, the naphthalene rings are essentially planar. The cyclohexane ring exhibits a puckered conformation, with puckering parameters [45], q 2 = 0.014 (6) (Figure 3). The bond distances and angles observed in the H 2 L 9 molecule is consistent with those reported for the other similar thiourea derivative [25]. It appears that this intramolecular hydrogen bonding is also present in the solution state. We base this conclusion on both the IR and NMR evidence cited above and the coordination behavior of the investigated compound. These thiourea derivatives have one imine group like N,N-dialkyl-N'benzoylthioureas [1][2][3][4][5]. These compounds easily coordinate to a metal atom via both sulfur and oxygen atoms. However, for the title type thiourea compounds [R(Ar)-CO-NH-CS-NH-R(Ar)] we observe that the carbonyl oxygen atom of the thiourea derivatives does not participate in the coordination with transition metal atoms because of the strong N-H•••O intramolecular hydrogen bond [26].  [46].

General
All chemicals used for the preparation of the compounds were of reagent grade quality. The room temperature attenuated total reflection Fourier transform infrared (FT-IR ATR) spectra of the all synthesized compounds were registered using a Varian FTS1000 FT-IR spectrometer with a Diamond/ZnSe prism (4000-525 cm −1 ; number of scans: 250; resolution: 1 cm −1 ). All 1 H-NMR spectra were recorded on a Bruker DPX-400 spectrometer, using CDCl 3 as the solvent and TMS as an internal standard. C, H and N analyses were carried out on a Carlo Erba MOD 1106 elemental analyzer. Single crystal X-ray data were collected on a Rigaku Mercury AFC8S system with a Mercury CCD detector using graphite-monochromated MoK α radiation (λ = 0.71073 Å). The structure was solved by direct methods and refined by using full-matrix least-squares techniques (on F 2 ) [47]. Data were corrected for Lorentz and polarization effects and for absorption. The latter correction was made using REQABA, a multi-scan technique [48]. All non-hydrogen atoms were refined anisotropically. Further details concerning data collection and refinement are given in Table 1.

Synthesis of the compounds
The compounds were prepared by a procedure similar to that reported in the literature [1][2][3][4][5]22]. A solution of cyclohexanecarbonyl chloride (0.005 mole) in acetone (50 mL) was added dropwise to a suspension of potassium thiocyanate (0.005 mole) in acetone (50 mL). The reaction mixture was heated under reflux for 30 min, and then cooled to room temperature. A solution of the appropriate primary amine (0.005 mole) (2-chlorobenzenamine, 3-chlorobenzenamine, 4-chlorobenzenamine, otoluidine, p-toluidine, 3-methoxybenzenamine, 4-methoxybenzenamine, and naphthalen-1-amine) in acetone (30 mL) was added to the mixture for 15 min at room temperature and stirred for 2 h. Hydrochloric acid (0.1 N, 300 mL) was added and the solution was filtered. The solid product was washed with water and purified by recrystallization from an ethanol-dichloromethane mixture (1:2).