Journal of the Pharmaceutical Society of Korea 21， 146-158 (1977)
The Crystal and Molecular Structure of
^-Cyclohexyl-A^ Co-Chlorobenzal) Imino Thiourea
C h u n g H o e K o o ， H o j i n g K i m H o o n S u p K i m a n d C h o n g W h a n C h a n g
Department o f Chemistry, College o f N a tu ra l Sciences，Seoul N ational University, Seoul 151
(Received June 28, 1977)
Abstract—iVi-Cyclohexyl-iV2~Co-chlorobenzaO imino thiourea, C14H18
N 3SCI, crystallizes in C2/C, with a =19. 68, b=7.74, c=20. 42A, !8=
92. 8° and eight formula units in the unit cell. The structure was solved by the study of Patterson sections, calculated from three-dimensional film data, and was refined by block-diagonal least-squares methods to R = 0 .16 based on 1288 independent intensity data. The rest atoms of iVi-cyclohexyl-iV2~Co-cholorobenzal) imino thiourea molecule excluding cyclohexan ring and chlorine atoms approximately lie on a plane. A pair of molecules related by the symmetry centers are connected directly with the N-H S hydrogen bonds. Apart from the hydrogen bonding system the structure is held together by the van der Waals forces.
A large number of aromatic and heterocyclic thiosemicarbazone derivatives with antibacte
rial and antitumor activity were reported by French, et a l.1^ Their hypothesis was that a thiosemicarbazone which could function as a tridentate chelate capable of form ing octahedral complexes with metal ions would possess antibacterial and antitumor activity. M uch later M athew and Palenik4) showed, by precision X-ray diffraction studies, the octahedral form ula
tion to be correct for bis(isoquinoline-l-carboxaldehyde thiosemicarbazanato nick e l(II) mon- ohydrate. They found the two ligands tridentately bound in two orthogonal planes.
A comparison of the results of Palenik and coworker's55 structural studies on antitumor active 5-hydroxy-2-formylpyridine thiosemicarbazone sesquihydrate and inactive acetone thio
semicarbazone with the available structural data on other thiosemicarbazones suggested some generalizations regarding the electronic structures, complexing abilities and biological activities- of thiosemicarbazones. They suggested that planar mono-negative tridentate nature of thio
semicarbazones appears to be an essential feature for the activities.
Apparently a knowledge of conformation and bond lengths and angles which result from structure analysis could be much meaninigful for the study of biological activity. Therefore”
a crystal structure analysis of iVi-cyclohexyl-iV^Co-chlorobenzal) im ino thiourea was undertaken as part of a program devoted to explain the relationship between three dimensional structure of thiosemicarbazone and its biological activities.
E X P E R IM E N T A L
Suitable evenly developed single crystals were grown by slow evaporation from a solution of Ny A^-dimethyformamide at room temperature. Oscillation and Weissenberg photographs were taken with crystals mounted along the b and c axes respectively w ith C u K a radiation.
The unit cell dimensions were determined from the two zero-layer Weissenberg photographs, on which the diffraction lines of alum inium foil were superposed for calibration.
The density of crystal was measured by the floatation method in a m ixture of benzene and carbon tetrachloride and agrees well w ith calculated value.
Crystal data:
A^i-Cyclohexyl-A^Co-chlorobenzal) im ino thiourea, C14H18N3SCI. M W = 259. 8. monoclinic, 沒二 19.68土0 .05， 노二7. 74±0. 03，c = 2 0 . 4 2 ± 0 .05 入，/3=92. 8土0. 30，
V —1691 A 3, D m= 1 .2 6 , D x 二 1 .2 6 g cm-3, Z 二 8
Systematic absences (hkZ for h + k ~ 2 n-f-1, hOZ for 1—2 n+ 1 and h = 2 n + 1 and OkO for k —2 n + l)
were consistent w ith space groups Cc and C2/C. The centric space group was confirm ed by the successful solution and refinement of the structure.
For determination of the structure, intensity data were collected w ith C u K a radiation fo r layers hkZ, k = 0 to 6 and hkl9 1= 0 and 1， by m ounting the crystals about the b and c axes，
respectively with an equi-inclination Weissenberg goniometer, using the m ultiple film technique.
The relative intensities were estimated visually w ith aid of a set of graded intensities recor
ded for the same specimen. A total of 1288 independent reflections was observed. The inten
sities were corrected for the spot-shape, Lorentz and polarization factors. N o corrections either for absorption or extinction were made.
The intensities were then scaled to a common base by correlating various layers. A n overall scale factor 13.9 and overall temperature factor B = 2 . 45 A2 were computed by W ilso n's method6).
ST R U C T U R E D E T E R M IN A T IO N A N D R E F IN E M E N T
A three-dimensional sharpened Patterson synthesis was evaluated, and the prom inent peaks on Harker section and line were easily interpreted as Cl-Cl vectors. A structure factor calcu
lation w ith chlorine contribution alone gave an R index of 0.54. T he possible positions for the S atoms could be deduced from a chlorine-phased electron density map on (h0/) calculated w ith 128 reflections. The R index based on the chlorine and sulfur atoms was 0.49 for the 1044 reflections. A subsequent three-dimensional Fourier synthesis showed the nineteen peaks
which were consistent with a chemically reasonable model for the molecule. A t this stage the structure factor calculation for 19 atoms gave a discrepancy index R二0.35, with a uniform isotropic temperature factor, 2.45 人2.
Then the structure was refined isotropically using an IB M 1130 block-diagonal least-squares program by Shiono(1968)7). The quantity minimised was X]w(|F0| — |FC|)2. The weighting scheme proposed by Cruickshank(1965)8) was used throughout the refinement. The form of the function, w, was (a-f-1F01 +c | F 012) -1, where a = 2 | F min| =：4 0 .10 and c = 2 /| F max| = 0 .0 0 7 and the refinement was terminated where none of the parameter shifts exceeded one sixth of the corresponding estimated standard deviations. Final R index is 0.16 for all observed reflections.
The positional and thermal parameters for the non-hydrogen atoms together w ith their • estimated standard deviations are listed in Table I. A tom ic scattering factor values were taken from the International Table for X-ray crystallography9). The observed and calculated structure factors of the observed reflections are listed in Table II.
R E S U L T A N D D IS C U S S IO N
The bond lenths and angles are given in Table I I I and Fig. 1 where the numbering of the atoms is indicated.
Table I -Final atomic coordinates and isotropic thermal parameters. The estimated standard deviations given in parentheses refer to the last decimal positions
X y z B (A )
Cl 0.496(1) 0.014(3) 0.654CO 2.0CO
s 0.236C1) 0.617C3) 0 .405CO 3.0(3)
NCD 0.364(2) 0.614(8) 0.372C2) 2CD
NC2) 0.351(2) 0.701C8) 0 .476C2) 2C1)
NC3) 0 .419C2) 0.715C® 0.485C2) 2C1)
CCO 0.550(5) 0.936(15) 0.598(5) 8(3)
c ⑵ 0.617(3) 0.933(9) 0.608(2) 3CD
CC3) 0.662(3) 0.866CL0) 0.564C3) 3CO
CC4) 0.637C® 0.762(10) 0.512(3) 3(1)
CC5) 0.563(3) 0.728(10) 0.505(3) 30D
CC6) 0.519C3) 0.823C10) 0.546C3) 2C1)
CC7) 0.440(3) 0.797(9) 0.536(3) 2(1)
C ⑧ 0.324(3) 0.650(10) 0.414(3) 2(1)
CC9) 0.349(3) 0.551(10) 0.305(3) 3CD
CC10) 0.410(2) 0.461(9) 0.279(2) 2(9)
c e i l ) 0.394(5) 0.392(15) 0.204(14) 7 ⑵
CC12) 0.377(4) 0.543(12) 0.163(3) 4CD
CC13) 0.317C4) 0.643C12) 0.190(3) 4(2)
CC14) 0.327(4) 0.698(13) 0.257C4) 5(2)
h=23 k = l h= 8 k = 0
123.14 104.04 141.42 118.67 208.44 191.28
81.64 70.63 21.43 14.48 41.91 33.05 17.05 11.99 34.61 26.39 9.72 6.18 h=10 k = 0 2 119.50 4 112.97 6 157.39 8 64.10 10 214.26 12 55.95 16 33.96 22 23.98
h = 0 k == 0 4 39.13 35.03 6 49.77 45.47
8 45.17 36.46
10 67. Z6 54.11 12 36.74 28.58 16 65.68 50.08 20 46.47 36.65
h=2 k == 0
h = 2 k = 2 0 68.8b 61.20 h=13 k = l
Table 11-Observed and calculated structure factors. Columns are: Index, Fobs，F cai
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