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Acta Cryst. (2008). E64, o610-o611    [ doi:10.1107/S1600536808004728 ]

(±)-N-[4-Acetyl-5-methyl-5-(4-methylcyclohex-3-enyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl]acetamide

T. Mohammed, N. Mazoir, J.-C. Daran, M. Berraho and A. Benharref

Abstract top

The new title thiadiazole compound, C14H21N3O2S, was semi-synthesized starting from 1-(4-methylcyclohex-3-enyl)ethanone, a natural product isolated from Cedrus atlantica essential oil. The stereochemistry has been confirmed by single-crystal X-ray diffraction. The thiadiazoline ring is roughly planar, although it may be regarded as having a half-chair conformation. The cyclohexenyl ring has a half-chair conformation. The most interesting feature is the formation of a pseudo-ring formed by four molecules associated through N-H...O hydrogen bonds around a fourfold inversion axis, forming an R44(28) motif.

Comment top

Thiadiazolic compounds have beenreported in a large number of papers (Beatriz et al., 2002, Farghaly et al., 2006). These compounds are associated with diverse biological activities. Likewise, the 1,3,4-thiadiazoles nuclei which incorporate toxiphoric –N=C—S– linkage possess anti-inflammatory (Udupi et al., 2000), herbicidal (Nizamuddin et al., 1999), antimicrobial (Demirbas et al., 2005) bactericidal (Sun et al., 1999) and anti-HIV-1 properties(Invidiata et al., 1996).

In this connection, the chemical modification of a natural product isolated from Cedrus atlantica essential oil, 1-(4-methylcyclohex-3-enyl) ethanone, using thiosemicarbazide (Paolo et al., 2005; Ourhriss et al., 2005; Aly et al., 2007) followed by treatment of acetic anhydride and pyridine yielded the 1,3,4-thiadiazolic compound (II) with a good yield and high chimiospecifity.

The structure of (II) was established by 1H and 13CNMR and confirmed by its single-Crystal X-ray structure (Fig. 1).

The thiadiazoline ring may be regarded as having a half-chair conformation with puckering parameters Q= 0.184 (1) Å and φ= 34.1 (4)° (Cremer & Pople, 1975); however it could be also considered as roughly planar with the largest deviation from the mean plane being -0.1069 (8) Å at N1. Such conformation is usual for thiadiazoline rings (Kubota et al., 1982; Radul et al., 2005). The cyclohexenyl ring has a half-chair conformation with puckering parameters Q=0.489 (2) Å, θ= 49.5 (2)° and φ= 344.8 (3)°.

The most interesting feature is the formation of a pseudo ring formed by four molecules associated through N—H···O hydrogen bonds around a fourfold screw axis (Fig. 2, Table 1) so completing a R44(28) motif (Etter et al., 1990; Bernstein et al., 1995).

Related literature top

For related literature, see: Aly et al. (2007); Beatriz et al. (2002); Bernstein et al. (1995); Cremer & Pople (1975); Demirbas et al. (2005); Etter et al. (1990); Farghaly et al. (2006); Invidiata et al. (1996); Kubota et al. (1982); Nizamuddin et al. (1999); Ourhriss et al. (2005); Paolo et al. (2005); Radul et al. (2005); Sun et al. (1999); Udupi et al. (2000).

Experimental top

To a solution of an equimolecular quantity of compound (I) and thiosemicarbazide dissolved in ethanol, several drops of HCl (c) were added. The reactional mixture was heated at reflux during 5 h and then evaporated under reduced pressure. The residue obtained was analysed on silica gel column with hexane: ethyl acetate (95:5) as an eluent. 0.25 mmol of the thiosemicarbazone obtained was dissolved in 2 ml of pyridine and 2 ml of acetic anhydride. The mixture was heated at reflux during 1 h with magnetic stirring, and then evaporated under reduced pressure. The residue obtained was purified on a silicagel column using hexane-ethyl acetate (90:10) as an eluent yielded compound (II) in 60% yield. Suitable crystals were obtained by evaporation of a dichloromethane solution at 277 K. m.p.= 483–484 K (dichloromethane); Spectroscopic analysis: 1H NMR (300 MHz, CDCl3) δ (p.p.m.): 9.49 (NH, s), 1.80 (3H2, s), 2.07 (1H1', m), 5.57 (1H3', dd, J1 = 10 Hz, J2 = 6 Hz), 1.58 (3H-7', s), 2.13, 2.27 (CH3CO, 2 s); 13C NMR (75 MHz, CDCl3) δ (p.p.m.): 85.4 (C-1), 19.2 (C-2), 36.7 (C-1'), 26.2 (C-2'), 118.1 (C-3'), 132.7 (C-4'), 28.2 (C-5'), 23.0 (C-6'), 22.2 (C-7'), 158.1 (C=N), 169.5, 170.4 (COCH3), 22.6, 24.5 (COCH3).

Refinement top

All H atoms attached to C and N atoms were fixed geometrically and treated as riding, with C—H = 0.95 (aromatic), 0.98 (methyl) or 0.99 Å(methylene) and N—H = 0.88 Å, with Uiso(H) = 1.2Ueq(C,N) or 1.5Ueq(methyl C).

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2 (Bruker, 2006; data reduction: APEX2 (Bruker, 2006; program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996), ORTEP-3 for Windows (Farrugia, 1997) and CAMERON (Watkin et al., 1993); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top
[Figure 1] Fig. 1. The molecular view of compound (II), showing the atom-labelling scheme. Ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. Projection down the c axis, showing the formation of the R44(28) motif through N—H···O hydrogen bonds around the fourfold screw axis 4. H atoms not involved in hydrogen bonding have been omitted for clarity.
[Figure 3] Fig. 3. The formation of the title compound.
(±)-N-[4-Acetyl-5-methyl-5-(4-methylcyclohex-3-enyl)-4,5-dihydro-\ 1,3,4-thiadiazol-2-yl]acetamide top
Crystal data top
C14H21N3O2SZ = 16
Mr = 295.40F000 = 2528
Tetragonal, I41/aDx = 1.287 Mg m−3
Hall symbol: -I 4adMo Kα radiation
λ = 0.71073 Å
a = 16.6855 (3) ÅCell parameters from 9915 reflections
b = 16.6855 (3) Åθ = 2.5–36.1º
c = 21.8961 (8) ŵ = 0.22 mm−1
α = 90ºT = 180 (2) K
β = 90ºPlatelet, colourless
γ = 90º0.29 × 0.24 × 0.08 mm
V = 6096.0 (3) Å3
Data collection top
Bruker APEXII CCD area-detector
diffractometer		3849 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.032
Monochromator: graphiteθmax = 30.5º
T = 180(2) Kθmin = 2.4º
φ and ω scansh = −23→23
Absorption correction: nonek = −23→23
87517 measured reflectionsl = −31→31
4637 independent reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.037H-atom parameters constrained
wR(F2) = 0.113  w = 1/[σ2(Fo2) + (0.0505P)2 + 5.869P]
where P = (Fo2 + 2Fc2)/3
S = 1.11(Δ/σ)max = 0.001
4637 reflectionsΔρmax = 0.39 e Å−3
185 parametersΔρmin = −0.26 e Å−3
Primary atom site location: structure-invariant direct methodsExtinction correction: none
Crystal data top
C14H21N3O2Sγ = 90º
Mr = 295.40V = 6096.0 (3) Å3
Tetragonal, I41/aZ = 16
a = 16.6855 (3) ÅMo Kα
b = 16.6855 (3) ŵ = 0.22 mm−1
c = 21.8961 (8) ÅT = 180 (2) K
α = 90º0.29 × 0.24 × 0.08 mm
β = 90º
Data collection top
Bruker APEXII CCD area-detector
diffractometer		4637 independent reflections
Absorption correction: none3849 reflections with I > 2σ(I)
87517 measured reflectionsRint = 0.032
Refinement top
R[F2 > 2σ(F2)] = 0.037Δρmax = 0.39 e Å−3
wR(F2) = 0.113Δρmin = −0.26 e Å−3
S = 1.11Absolute structure: ?
4637 reflectionsFlack parameter: ?
185 parametersRogers parameter: ?
H-atom parameters constrained
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.65060 (7)0.64068 (7)0.33934 (6)0.0214 (2)
C20.64575 (8)0.56723 (8)0.29765 (6)0.0287 (3)
H2A0.68000.57550.26180.043*
H2B0.59020.55940.28440.043*
H2C0.66390.51970.32000.043*
C30.68632 (7)0.78535 (7)0.31834 (6)0.0211 (2)
C110.79352 (7)0.62428 (7)0.37378 (6)0.0235 (2)
C120.87096 (7)0.66585 (8)0.38792 (7)0.0281 (3)
H12A0.90940.62700.40430.042*
H12B0.86150.70810.41820.042*
H12C0.89260.68970.35050.042*
C310.62901 (8)0.90880 (8)0.27886 (6)0.0270 (2)
C320.64169 (10)0.99767 (9)0.27574 (10)0.0446 (4)
H32A0.66341.01200.23560.067*
H32B0.67961.01400.30760.067*
H32C0.59041.02520.28200.067*
C1'0.61004 (7)0.62529 (7)0.40168 (6)0.0230 (2)
H1'0.63420.57540.41900.028*
C2'0.52001 (8)0.61027 (9)0.39510 (6)0.0298 (3)
H2E0.49500.65670.37430.036*
H2F0.51140.56240.36930.036*
C3'0.47984 (9)0.59770 (10)0.45606 (7)0.0360 (3)
H3'0.43070.56900.45780.043*
C4'0.51280 (9)0.62689 (10)0.50920 (7)0.0351 (3)
C5'0.58895 (11)0.66893 (12)0.50955 (7)0.0433 (4)
H5A0.62870.63490.53090.052*
H5B0.58250.71840.53400.052*
C6'0.62334 (9)0.69185 (9)0.44820 (6)0.0309 (3)
H6A0.68150.70230.45240.037*
H6B0.59750.74170.43360.037*
C7'0.47125 (12)0.61447 (13)0.56956 (8)0.0504 (4)
H710.42310.58180.56340.076*
H720.45610.66650.58670.076*
H730.50760.58690.59780.076*
S10.604309 (17)0.726031 (18)0.298610 (14)0.02284 (9)
O10.78216 (6)0.55218 (6)0.38435 (5)0.0313 (2)
O20.57194 (6)0.87583 (6)0.25536 (5)0.0338 (2)
N10.73445 (6)0.66905 (6)0.34821 (5)0.0224 (2)
N20.74763 (6)0.75163 (6)0.34255 (5)0.0231 (2)
N30.68691 (6)0.86761 (6)0.31029 (5)0.0251 (2)
H30.72680.89510.32630.030*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0182 (5)0.0197 (5)0.0262 (5)−0.0009 (4)−0.0014 (4)−0.0010 (4)
C20.0296 (6)0.0251 (6)0.0312 (6)−0.0016 (5)−0.0005 (5)−0.0063 (5)
C30.0177 (5)0.0211 (5)0.0245 (5)−0.0012 (4)0.0000 (4)0.0011 (4)
C110.0200 (5)0.0228 (5)0.0277 (6)0.0034 (4)−0.0003 (4)0.0000 (4)
C120.0202 (5)0.0264 (6)0.0376 (7)0.0022 (4)−0.0047 (5)0.0019 (5)
C310.0242 (6)0.0267 (6)0.0302 (6)0.0032 (4)0.0007 (5)0.0060 (5)
C320.0397 (8)0.0253 (7)0.0687 (12)0.0039 (6)−0.0089 (8)0.0114 (7)
C1'0.0211 (5)0.0236 (5)0.0244 (5)−0.0011 (4)−0.0006 (4)0.0008 (4)
C2'0.0239 (6)0.0370 (7)0.0287 (6)−0.0066 (5)−0.0005 (5)0.0027 (5)
C3'0.0288 (7)0.0432 (8)0.0359 (7)−0.0025 (6)0.0059 (5)0.0077 (6)
C4'0.0340 (7)0.0396 (8)0.0318 (7)0.0040 (6)0.0066 (6)0.0060 (6)
C5'0.0507 (9)0.0514 (9)0.0278 (7)−0.0088 (7)0.0052 (6)−0.0059 (6)
C6'0.0320 (7)0.0322 (7)0.0286 (6)−0.0054 (5)0.0009 (5)−0.0046 (5)
C7'0.0547 (11)0.0607 (11)0.0360 (8)−0.0001 (9)0.0146 (8)0.0057 (8)
S10.01844 (14)0.02350 (15)0.02657 (15)−0.00176 (10)−0.00422 (10)0.00242 (10)
O10.0263 (4)0.0217 (4)0.0460 (6)0.0025 (3)−0.0046 (4)0.0038 (4)
O20.0284 (5)0.0368 (5)0.0361 (5)0.0003 (4)−0.0088 (4)0.0073 (4)
N10.0171 (4)0.0185 (4)0.0316 (5)0.0000 (3)−0.0017 (4)0.0015 (4)
N20.0183 (4)0.0195 (4)0.0314 (5)−0.0011 (3)−0.0014 (4)0.0024 (4)
N30.0200 (5)0.0208 (5)0.0345 (6)−0.0007 (4)−0.0038 (4)0.0035 (4)
Geometric parameters (Å, °) top
C1—N11.4897 (15)C32—H32C0.9800
C1—C21.5303 (17)C1'—C6'1.5232 (18)
C1—C1'1.5451 (17)C1'—C2'1.5298 (17)
C1—S11.8493 (12)C1'—H1'1.0000
C2—H2A0.9800C2'—C3'1.508 (2)
C2—H2B0.9800C2'—H2E0.9900
C2—H2C0.9800C2'—H2F0.9900
C3—N21.2822 (15)C3'—C4'1.376 (2)
C3—N31.3839 (15)C3'—H3'0.9500
C3—S11.7431 (12)C4'—C5'1.451 (2)
C11—O11.2396 (15)C4'—C7'1.507 (2)
C11—N11.3577 (15)C5'—C6'1.510 (2)
C11—C121.4987 (18)C5'—H5A0.9900
C12—H12A0.9800C5'—H5B0.9900
C12—H12B0.9800C6'—H6A0.9900
C12—H12C0.9800C6'—H6B0.9900
C31—O21.2141 (17)C7'—H710.9800
C31—N31.3710 (16)C7'—H720.9800
C31—C321.499 (2)C7'—H730.9800
C32—H32A0.9800N1—N21.4009 (14)
C32—H32B0.9800N3—H30.8800
N1—C1—C2112.45 (10)C3'—C2'—C1'112.07 (12)
N1—C1—C1'110.42 (10)C3'—C2'—H2E109.2
C2—C1—C1'111.76 (10)C1'—C2'—H2E109.2
N1—C1—S1102.15 (7)C3'—C2'—H2F109.2
C2—C1—S1107.88 (9)C1'—C2'—H2F109.2
C1'—C1—S1111.79 (8)H2E—C2'—H2F107.9
C1—C2—H2A109.5C4'—C3'—C2'121.44 (13)
C1—C2—H2B109.5C4'—C3'—H3'119.3
H2A—C2—H2B109.5C2'—C3'—H3'119.3
C1—C2—H2C109.5C3'—C4'—C5'121.69 (14)
H2A—C2—H2C109.5C3'—C4'—C7'120.61 (15)
H2B—C2—H2C109.5C5'—C4'—C7'117.69 (15)
N2—C3—N3118.82 (11)C4'—C5'—C6'116.78 (14)
N2—C3—S1118.67 (9)C4'—C5'—H5A108.1
N3—C3—S1122.49 (9)C6'—C5'—H5A108.1
O1—C11—N1119.99 (11)C4'—C5'—H5B108.1
O1—C11—C12122.86 (11)C6'—C5'—H5B108.1
N1—C11—C12117.15 (11)H5A—C5'—H5B107.3
C11—C12—H12A109.5C5'—C6'—C1'110.78 (12)
C11—C12—H12B109.5C5'—C6'—H6A109.5
H12A—C12—H12B109.5C1'—C6'—H6A109.5
C11—C12—H12C109.5C5'—C6'—H6B109.5
H12A—C12—H12C109.5C1'—C6'—H6B109.5
H12B—C12—H12C109.5H6A—C6'—H6B108.1
O2—C31—N3122.57 (12)C4'—C7'—H71109.5
O2—C31—C32122.65 (13)C4'—C7'—H72109.5
N3—C31—C32114.79 (12)H71—C7'—H72109.5
C31—C32—H32A109.5C4'—C7'—H73109.5
C31—C32—H32B109.5H71—C7'—H73109.5
H32A—C32—H32B109.5H72—C7'—H73109.5
C31—C32—H32C109.5C3—S1—C189.42 (5)
H32A—C32—H32C109.5C11—N1—N2117.63 (10)
H32B—C32—H32C109.5C11—N1—C1124.11 (10)
C6'—C1'—C2'109.00 (11)N2—N1—C1116.65 (9)
C6'—C1'—C1113.93 (10)C3—N2—N1110.05 (10)
C2'—C1'—C1111.97 (10)C31—N3—C3123.79 (11)
C6'—C1'—H1'107.2C31—N3—H3118.1
C2'—C1'—H1'107.2C3—N3—H3118.1
C1—C1'—H1'107.2
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N3—H3···O1i0.881.952.8223 (14)171
Symmetry codes: (i) y+1/4, −x+7/4, −z+3/4.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N3—H3···O1i0.881.952.8223 (14)171
Symmetry codes: (i) y+1/4, −x+7/4, −z+3/4.
Acknowledgements top

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references
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